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Evidence is provided which supports the concept that a previously characterized monoclonal IgA-λ rheumatoid factor with a medium-binding avidity reacts with a select Fc region antigenic determinant. The interaction between this rheumatoid factor and anti-Rh-coated human erythrocytes is inhibited by IgG1 Fc fragment, IgG1 heavy chains, and a single peptide pool isolated from this tryptic digest by paper chromatography. Cyanogen bromide cleavage of the isolated heavy chains abolishes this reactivity. A methionine residue is assumed to be near, involved in, or necessary for reactivity between the IgA and its antigenic determinant. The data thus provide further evidence for a specific autoantigenic, rheumatoid factor-reactive determinant. [ABSTRACT FROM AUTHOR]

Mitogen-transformed human peripheral blood lymphocytes and tonsil blasts were examined by rosette formation to detect the presence of membrane-bound immunoglobulin (Ig) and surface receptors for fixed IgG and fixed C3. In addition, the capacity of these cells to rosette with sheep erythrocytes was evaluated as a reaction characteristic of T lymphocytes. In order for clear morphological recognition of the rosetting transformed lymphocytes and the rosetting tonsil blasts a cytocentrifuge technique was developed and used in conjunction with autoradiography and/or with Romanowsky stains. Using these techniques and the culture methods described in this paper phytohaemagglutinin, pokeweed mitogen, streptococcal filtrates and purified protein derivative stimulated predominantly T cells in the peripheral blood of man. A minority of the transformed cells in these mitogen-stimulated cultures (<24%) did rosette with B lymphocyte markers and presumably represent a B-cell response. No significant differences were found between the T- or B-cell specificity of the mitogens investigated. Lymphoid preparations from tonsils excised from normal donors with recurrent tonsillitis were found to contain 6-15% lymphoblasts and the iarge majority of these cells formed rosettes with the B-cell markers, less than 20% of these lymphoblasts formed spontaneous sheep erythrocyte rosettes. Using a mixed rosetting technique a small proportion (<5%) of PHA-transformed cells and tonsil lymphoblasts were found to have combined sheep Fc or combined sheep C3 receptors. The investigation of B- and T-lymphocyte surface markers on mitogentransformed lymphocytes was extended to neopiastic lymphocyte populations and it was found that the majority of transformed cells (>70%) present in chronic lymphocytic leukaemia cultures stimulated with PHA after 6 days incubation were transformed T lymphocytes. [ABSTRACT FROM AUTHOR]

This paper confirms results showing that TA3 tumour cells coated in vivo with immunoglobulins, lose some of the coat upon transfer to in vitro conditions. By labelling IgG isolated from the ascitic fluid of TA3 tumours it was found that the immunoglobulin coating TA3 cells is dynamically exchanged with immunoglobulin in the corresponding ascitic fluid. Some of the released immunoglobulin is in a degraded state as judged from the fact that most of the released material lost the antigenicity of intact immunoglobulin and has a lower capacity to precipitate with ammonium sulphate at 50% saturation. The degraded immunoglobulin has a higher binding efficiency to tumour cells. In vivo experiments demonstrated that the ascitic fluid of mice bearing TA3 and MCIM tumours contains a material which has some of the physicochemical properties of IgG but which does not precipitate with antisera directed aguinst IgG. [ABSTRACT FROM AUTHOR]

In this paper the specificity of the skin-reactive guinea-pig immunoglobulin in the homologous PCA test has been reconsidered. Extensive purification of this immunoglobulin by chromatographic methods results in the isolation of a small fraction or medium speed immunoglobulins that contains all skin reactivity. No correlation could be found with the 7S immunoglobulins IgGγ1 and Igγ1A suggesting a separate class of biologically active immunoglobulins. The PCA active antibody belongs to either an IgG subclass or is a heat stable homocytotropic antibody. Rabbit and chicken antisera against isolated fractions of guinea-pig immunoglobulins show the existence of 7S subclasses. Some suggestions for a revised nomenclature are given. [ABSTRACT FROM AUTHOR]

The article presents information on IgM-IgG cryoglobulinaemia with IgM paraprotein component. Four patients with mixed IgM-IgG cryoglobulinaemia are described. Clinically they all had some features of an autoimmune disease, while two of them had a lympho-epithelial tumor in the parotid gland. The term paraprotein is used in this article for electrophoretically homogeneous immunogiobulins, which belong to only one light chain type. It implies no further assumptions about their nature and origin. It is the intention of this paper to report in detail the clinical and biochemical findings in four patients with IgM-IgG cryoglobulins, the IgM part of which had the characteristics of a paraprotein with anti-IgG activity.

The results of 51Cr red cell survival and organ sequestration studies in seventy-six patients with autoimmune haemolytic anaemia are described. In patients with incomplete IgG and IgA warm autoantibodies increased red cell destruction to a varying degree and mainly spleen sequestration were found. In patients with IgM incomplete warm autoantibodies sequestration of red cells mainly in the liver was seen. Liver sequestration was also present in patients with cold agglutinins/haemolysis, sometimes accompanied by a significant spleen sequestration. In a number of patients with haemolytic autoantibodies, i.e. warm haemolysins and cold agglutinins/haemolysins, a biphasic 51Cr elimination curve was obtained. The cause of this type of survival curve is discussed. In patients in whom a positive direct anticomplement test was the only serological abnormality a normal 51Cr red cell life-span was found. [ABSTRACT FROM AUTHOR]

This article presents information on a patient with the association of cryoblobulinaemia and cold urticaria. The cryoglobulin was exclusively kappa type IgG. The cold urticaria was passively transferred to nortnal recipients utilizing the isolated cold precipitable IgG and the cryoprotein-containing whole serum. Physical examination demonstrated only bilateral ankle pigmentation and readily producible cold urticaria. The following pertinent laboratory data were either negative or normal: Haemogram, serologic test for syphilis, urinalysis. sedimentation rate, cloning factor evaluation, cold agglutinins, cold haemoiysins, Sia test, latex tixation agglutination test, liver function studies, renal function tests. Bence Jones proteinuria. numerous bone marrow aspirations and roentgenologicai studies of the chest, bones, entire gastrointestinal tract and kidneys.

Cytotoxicity was studied in a model system using chicken erythrocytes (Ch RBC) labelled with 51Cr as target cells and human peripheral blood lymphoid cells as effector cells. In vitro human lymphoid cells are highly efficient in destroying target cells coated with anti-target cell antibody, the mean net percentage cytotoxicity of lymphoid cells from fifty-eight control subjects being 64.27±206 (SEM). In the absence of antibody the mean net percentage cytotoxicity was 6.90± 0.46. As little as 10 ng rabbit anti-Ch RBC IgG was required to cause significant target cell lysis. Studies on the nature of the lymphoid cell-dependent cytotoxic antibody showed that it is localized in the 7S IgG region of whole serum and that an intact Fc region is required: the F(ab')2 fragment obtained by pepsin digestion of IgG was inactive although able to inhibit the cytotoxic activity of the whole undigested IgG. Investigation of the kinetics of LOAC showed chat when anti-body was added to the final culture medium target cell lysis progressed rapidly (detectable within 2 hr) and linearly with time up to 8 hr. Thereafter the rate of lysis decreased reaching a maximum after 12 hr culture. With cultures containing target cells which have been pre-incubated with antibody, lysis occurred even more rapidly. detectable within 30 min and reaching a maximum after only 3-4 hr culture. The maximum cytotoxicity in this system was, however, lower than that obtained when antibody was added directly to the culture medium. Cytotoxicity could be inhibited by the addition of aggregated human IgG. as little as 5 μg causing 100% inhibition target cell lysis. Study of the nature of die effector lymphoid cell showed, first. that viable cells were required, twice frozen/thawed lymphoid cell suspensions being inactive; secondly, that active protein synthesis by the effector cell was not an essential prerequisite. pretreatment or lymphoid cells with mitomycin C having no significan effect on their ability to lyse antibody-coated target cells but significantly resducing their ability to transform in response to the mitogen PHA; thirdly, that the effector cell is non-phagocytic, non-plastic or glass-adherent and does not bear surface immunoglobulin; and fourthly that significant cytotoxicity is detectable even with a total lymphoid cell to target cell ratio of 1:2. [ABSTRACT FROM AUTHOR]

Fractions of adult schistosomes (S. mansoni) were tested for their ability to absorb an IgG antibody activity which appears in the sera of rats and Rhesus monkeys infected with the parasite and is lethal to schistosomula cultured in vitro. The same fractions were tested for their immunogenicity in raising lethal antibody when administered to rats in Freund's adjuvant. The results of these experiments indicated that an antigen which both absorbs and induces the formation of lethal antibody is present almost entirely in the water-insoluble portion of adult schistosome homogenates. The antigen appears to be tightly bound to this membrane fraction since the use of strong anionic detergents is necessary in its extraction. Membranes solubilized in sodium dodecyl sulphate were fractionated by gel filtration on Sephadex columns equilibrated with the detergent. The same specific Sephadex fraction was shown to absorb both rat and Rhesus monkey lethal antibodies as well as induce the antibody when administered to rats. Further purification and analysis suggested that the immunogen was one of four proteins with molecular weights estimated between 21,000 and 33,000 Daltons. Rats vaccinated with partially purified antigen developed levels of lethal antibody similar to those found in animals immune to challenge through previous exposure to the parasite, yet were themselves only marginally resistant to infection. These results indicate that while clearly toxic to schistosomula grown in vitro, lethal antibody operating on its own in vivo is incapable of mediating the rejection of schistosome infections. [ABSTRACT FROM AUTHOR]

Sixteen patients with bullous pemphigoid were examined using direct and indirect immunofluorescent techniques with antisera specific for Clq, C4, C3, C5, C3 pro-activator, properdin, fibrinogen, IgA, IgM, IgG and IgE. The results of these studies are consistent with the activation of complement via the classical (antibody- Clq) sequence as well as via the alternate pathway. Fibrinogen and/or fibrin derivatives were demonstrated on the basement membrane of ten of fifteen patients tested and IgE basement membrane staining was found in four individuals. [ABSTRACT FROM AUTHOR]

Two siblings, a girl and a boy, and their mother were abnormally susceptible to infections with bronchopneumonias leading to chronic pulmonary atelectasis in the girl and otitis leading to necrotizing changes with deafness in the mother. The causative micro-organism most often found was Haemophilus influenzae. The serum IgG was within the normal concentration range, but showed restricted electrophoretic heterogeneity with absence of the anodal component. Serum IgG2 and lgG4 were absent. Absence of antibodies to teichoic acid and haemagglutinating antibodies to Haemophitus influenzae polysaccharide was noted as was the case with isohaemagglutinins and heteroagglutinins against sheep cells. Lymphopenia and poor [³H]thymidine uptake by peripheral lymphocytes after PHA stimulation were demonstrable in the girl and the mother. The girl had developed an epithelial ovarian tumour. The disease was a non-X-linked recessive and expressed selective humoral and selective cellular immunodeficiency. An inherited structural or regulatory gene defect is suggested. Gamma-globulin therapy had a good clinical effect. [ABSTRACT FROM AUTHOR]

The uptake of homologous lymphocytes by rat macrophages was observed in tissue culture chambers. This uptake was quantified as an opsonization index. The effect on this index of treatment of either lymphocytes or macrophages by horse anti-lymphocytic globulin (ALG) or normal horse IgG (N.IgG) in the presence or absence of complement was measured. ALG-treated lymphocytes were shown to attach to immune adherence receptors on human erythrocytes in the presence of complement. A complement attachment of ALG-treated lymphocytes to macrophages was also observed following blocking of cytophilic receptors by N.IgG. [ABSTRACT FROM AUTHOR]

A comparison has been made of several techniques for the preparation from antilymphocyte serum of pure antilymphocyle antibody by absorption on, and elution from mouse thymocytes. The best yield was obtained by a batch method using cells fixed in 0.1% formaldehyde as immunoabsorbent followed by elution with 0.12 M citrate buffer at pH 3.0. The antilymphocyte activity of eluates was studied in vitro by determination of membrane immunofluorescence titres and in vivo by the neutralization of the local renal xenogeneic graft-versus-host reaction. These tests showed that an IgG eluate of a rabbit antilymphocyte serum was nineteen times more active than the same weight of the whole IgG present in the parent serum. [ABSTRACT FROM AUTHOR]

Aggregation of human platelets (P1.A) induced by IgG immune complexes of rabbit (Ea-aEa, NIP2-24 BSA-aNIP) and human (tetanus toxoid-aT) origin and by heat-aggregated human polyclonal IgG was inhibitable by antiglobulin-active IgM components dissociated from IgM-IgG cryoglobulins. The inhibitory capacity of the Cryo-IgM components extended over a wide range of Ag:Ab ratios on both sides of the equivalence, and likewise over a wide range of epitope densities on the Ag portion of the P1.A active Ag--Ab complex. In contrast to the inhibitability of IgG complex-induced P1.A was the total lack of inhibition by Cryo-IgM components of P1.A induced by anti-platelet rabbit antibodies. The P1.A active IgG complexes inhibitable by Cryo-IgM were shown by sucrose gradient centrifugation analyses to be greater than 19S. This type of complexes was also present in a number of patient sera. It is concluded that the application of antiglobulin-active cryoglobulin IgM components in combination with the P1.A phenomenon provide a useful means for detection and analysis of circulating complexes and for differentiation of complex-induced P1.A from antibody-induced P1.A. [ABSTRACT FROM AUTHOR]

Hepatitis and other sera were studied for direct platelet aggregating (P1.A.) activity in non-heated and heat-treated state, for inhibitability of P1.A. by antiglobulin active cryoglobulin IgM components (Cryo-IgM), and for sedimentation velocity of P1.A. activity by sucrose gradient centrifugation. Three distinct patterns of direct P1.A. activity were established: (1) 'aggregated IgG type': heating-dependent, ≧ 9S, inhibitable by Cryo-IgM, serum anticomplementary; (2) 'antibody type': heating-independent, 7S and/or 19S, non-inhibitable by Cryo-IgM, serum not anticomplementary; and (3) 'immune-complex type': heating-independent, ≧19S, inhibitable by Cryo-lgM, anticomplementary activity present or absent. In the heavy P1.A.-active sucrose gradient serum fractions of one patient, only IgG4 Gm markers were detected. [ABSTRACT FROM AUTHOR]

The effect of procarbazine and cyclophosphamide on the formation of antibodies to sheep red blood cells in mice is investigated. Cyclophosphamide was found to have the best immunosuppressive effect when given after antigen; recovery from drug treatment was relatively fast; under experimental conditions that favour cyclophosphamide action (antigen prior to drug) IgM formation was found to be depressed and prolonged; IgG formation was markedly depressed or altogether missing. Procarbazine was found to act best when given prior to antigen; recovery was slow; under experimental conditions that favour procarbazine action (drug prior to antigen) the induction period was prolonged. IgM titres were slightly and IgG titres markedly depressed. Under all conditions tested procarbazine had little effect on the onset of IgG production. [ABSTRACT FROM AUTHOR]

IgG antiglobulins in human sera were measured by single radial diffusion in agar after elution from ethyl chloroformate insolubilized immunosorbents of rabbit or human IgG. With both immunosorbents seronegative and seropositive rheumatoid sera contained significantly higher levels of IgG antiglobulins than did sera from healthy adults. Attempts to measure antiglobulins interacting specifically with the pFc' half of the Fc region were not successful due to an unacceptably high degree of non-antibody binding. [ABSTRACT FROM AUTHOR]

Peripheral lymphocytes from thyrotoxic patients with detectable plasma LATS were cultured for 6 days with phytohaemagglutinin (PHA). LATS was found in the culture medium in seven of eleven cultures with PHA, but on only one occasion without PHA, and only once in the material extracted from the lymphocytes by freezing and thawing. LATS was not detected in the medium in which cells from normal people were cultured or when medium was incubated in the absence of cells. The LATS activity was neutralized by anti-IgG serum. That the LATS WUS produced by the cells during culture rather than released as antibody preformed iii vivo was confirmed by the absence of LATS in cultures of the cells frozen at the beginning of incubation. These findings provide further evidence that LATS is an immunoglobulin thereby strengthening the hypothesis that Graves' disease is an autoimmune disorder, [ABSTRACT FROM AUTHOR]

In the presence of normal human lymphocytes, decomplemented sera from twenty-nine out of thirty-nine patients with Hashimoto thyroiditis caused significant lysis of thyroglobulin-coated chicken red blood ceils, as estimated by the release of 51Cr; the mean % specific 51Cr release being 14.1 ± 1.9 (SEM). Serum from twenty-one control subjects studied concurrently caused no significant lysis of thyroglobulin-coated chicken red blood cells; the mean % specific 51Cr release being -1.6 ± 0.7 (SEM). The degree of cytotoxicity correlated with the titre of thyroglobulin antibodies in the serum, determined by tanned red cell haemagglutination. The active component in the Hashimoto serum was localized in the 19S fraction, was unaffected by pre-absorption with anti-human IgM serum, but was neutralized by preabsorption with anti-human IgG serum. These findings suggest that the cytotoxic activity of serum from patients with Hashimoto thyroiditis is due to the presence of thyroglobulin antibody of the IgG class in the form of complexes, either alone or with antigen. It is postulated that non-specific lymphocytes may play an important role in the pathogenesis of Hashimoto thyroiditis, being activated by the presence in the gland of thyroglobulin antibody, either alone or in the form of complexes attached to thyroid cells. [ABSTRACT FROM AUTHOR]

IgG-class iso-antibodies against human IgM ('reverse rheumatoid factors') were detected in titres from 1:4 to 1:1024 in the serum of twelve of forty subjects (30%) with selective IgA deficiency. The antibodies were detected in a haemagglutination system with red cells coated by the chromic chloride method with proteins from a panel including nineteen Waldenström macroglobulins. The forty subjects included seventeen normal subjects, ten with recurrent infections, seven with ataxia telangiectasia, two each with asthma and lymphoma and one each with rheumatoid arthritis and chronic active hepatitis. Four of the twelve positive sera contained 'class-specific anti-IgM' which reacted with all or most of the IgM coats. The eight sera containing 'anti-IgM of limited specificity' included six reacting with only one IgM coat, one reacting with two IgM coats and one reacting with four IgM coats. The anti-IgM in the latter serum defined an inherited allotypic marker on these four IgM proteins. There was no significant correlation between the presence of anti-IgM antibodies and the clinical status, sex and age of the patient nor the presence of antibodies against human IgG, human IgA and ruminant proteins. These antibodies against human IgM represent yet another immunologic abnormality in this group of patients. [ABSTRACT FROM AUTHOR]

Monoclonal immunoglobulins in serum and cerebrospinal fluid (CSF) were found in newborns with congenital toxoplasmosis. The M-components were of igG-class and of both κ and λ type. The monoclonal proteins were found in the serum of new- borns but not in the serum of their mothers. The monoclonal immunoglobulins were therefore selectively transferred or synthesized by the newborn. There was a local production or selective local accumulation of immunoglobulins in the cerebro- spinal fluid. The M-components disappeared and the IgM level in serum and cerebrospinal fluid decreased after therapy. IgA was found to be elevated between 2-4 months of age. CRP was elevated in the first weeks after birth but afterwards returned to normal. The Dye test localized antibody activity to the site of the M- components in the electrophoresis of both serum and cerebrospinal fluid. The Dye test antibodies of mothers' sera also showed restricted heterogeneity with about the same electrophoretic localization as in the children's sera. Rheumatoid factors were found in serum and CSF of newborns with congenital toxoplasmosis, but not in serum of their mothers. [ABSTRACT FROM AUTHOR]

Ig levels were determined by radial immunodiffusion in uncomplicated cases of acute hepatitis with or without Australia antigenaemia. Initial sera from Australia antigen negative cases showed a striking elevation in IgM levels when compared to Australia antigen positive cases (6.5 versus 1.9 mg/ml). None of twenty-four Australia antigen positive cases exceeded 3 mg/ml IgM, and only 3/58 Australia antigen negative cases exhibited values below 3 mg/ml. initial sera from Australia antigen positive and Australia antigen negative subjects did not differ in concentration of IgG, IgA, or IgD. Serial determinations of IgG revealed a transient fall in patients with Australia antigen positive hepatitis, and a rise in Australia antigen negative cases. Asymptomatic, Australia antigen positive, Guaymi Indian subjects were compared to matched Australia antigen negative controls from the same indigenous group and no differences in the concentration of IgG, IgM, IgA or IgD were found, although elevations of IgG and IgM were common in both groups. No evidence of abnormal proteins was found when sera were tested by cellulose acetate electrophoresis or by immunoelectrophoresis versus immunoglobulin-specific anti- sera. Ultracentrifugal analysis failed to detect `7S' IgM. [ABSTRACT FROM AUTHOR]

Antibodies in human sera against four different antigens of human spermatozoa discovered by means of an indirect two-layer immunofluorescence technique (IFT) were characterized by determination of the class of immunoglobulins to which they belonged. A three-layer IFT using monospecific antisera against human IgG, IgA or IgM as the second layer was employed together with fractionation of sera on Sephadex G-200 or DEAE-cellulose followed by testing of the concentrated pools in a two-layer IFT. The study revealed that antibodies against the antigen in the front part of the acrosome were primarily IgM and those against the antigen in the tail primarily IgG. Antibodies against antigens in the equatorial segment and the postnuclear cap showed a varying predominance of these two immunoglobulins. Spermatozoal antibody as IgA was found only in small amounts. [ABSTRACT FROM AUTHOR]

Metabolic turnover studies were performed with radio-iodinated IgG in twelve patients with a serum IgG level greater than 1600 mg/100 ml (six with monoclonal gammopathy and six with a polyclonal increase in IgG associated with liver disease). The six patients with an IgG monoclonal protein comprised four multiple myeloma, one benign monoclonal gammopathy and one biclonal gammopathy presenting as Waldenström's macroglobulinaemia. The six patients with liver disease comprised two patients with cirrhosis, two with infective hepatitis and two with chronic active hepatitis. The injected IgG was either autologous normal IgG (five cases), autologous monoclonal IgG (five cases), homologous normal IgG (one case) or therapeutic intravenous HGG (two cases). The plasma volume was increased in six patients; the plasma IgG pool in nine; and the total body IgG pool in seven. The plasma T½ was normal in one patient with monoclonal and one patient with polyclonal gammopathy but shortened in the other ten studies with mean values of 11.3 and 11.0 days in monoclonal and polyclonal gammopathy respectively. The fractional turnover rate was normal in two studies in polyclonal gammopathy and increased in the other ten with mean values of 13.6% per day in both groups of patients. The IgG synthesis rate was significantly increased in all studies except for a reduced synthesis of normal IgG in one patient with multiple myeloma. The mean synthesis rates in monoclonal and polyclonal gammopathy were respectively 6.7 and 4.1 times the mean synthesis rate in normal controls. The pattern of increased synthesis and increased catabolism in such patients confirms published reports in some diseases and demonstrates a similar pattern in chronic active hepatitis. The findings are consistent with the `concentration-catabolism' effect. [ABSTRACT FROM AUTHOR]

The concentration of IgG subclasses was measured in matched pairs of maternal and cord serum by single radial immunodiffusion. IgG1, IgG3 and IgG4 were present in similar amounts in both the mothers and infants. IgG2 was present in the mothers at about 3 times the amount in the cord blood. [ABSTRACT FROM AUTHOR]

The treatment of Carworth Wistar rats with normal equine IgG or ALG pre-absorbed with sheep erythrocytes sensitized the rats to sheep erythrocytes and prevented ALG from suppressing the primary immune response to this antigen. [ABSTRACT FROM AUTHOR]

Polyclonal Ig of one or other class was significantly reduced in 82% of subjects with monoclonal protein disease (MPD). Ig deficiency was equally frequent with all classes of monoclonal Ig, but was considerably more common in myelomatosis than in benign MPD. Polyclonal IgG isolated from sera containing monoclonal IgG, IgA or IgM was normal in regard to electrophoretic heterogeneity and proportions of κ- and γ-chains. Peripheral lymphoid. tissues from most patients within deficiency failed to synthesize the corresponding polyclonal Ig in vitro. Monoclonal protein was synthesized by macroglobulinaemic lymph node tissue, but monoclonal proteins were riot synthesized by nodes from subjects with, myelomatosis. Polyclonal Ig deficiency in macroglobulinaemia can be ascribed to peripheral spread of neoplastic cells, but the same process does not apparently account for Ig deficiency in typical cases of myelomatosis. [ABSTRACT FROM AUTHOR]

An immunochemical and serological study of a patient with rheumatoid arthritis who developed multiple myelorna and was treated with 1-phenylalanine mustard showed a striking difference in the effect of this drug on the rapidly dividing cells, as opposed to the resting plasma cells. The titres of anti-globulin antibodies such as the IgG serum agglutinators and the IgM rheumatoid factors were little altered although the IgG rnyeloma spike has disappeared following therapy. Fractionation of two different serum samples from 1966 and 1970 showed the IgG paraprotein to be serologically inactive for anti-globulin activity. This paraprotein was also characterized by producing only a single IgG precipitin line with horse anti-human whole serum antibody while the normal IgG globulins always showed a double line. [ABSTRACT FROM AUTHOR]

The nature of the heat precipitation of 3 mononoclonal heat labile immunoglobulins was studied. These included 2 γG pyroglobulins and one γM pyroglobulin. Thermoprecipitable activity of both γ3 pyroglobulins could be localized to their heavy chains and to the Fab fragments of one of them. Heat precipitability of the γM paraprotein required the presence of the intact γM molecule since 7S subunits did not precipitate. The thermal precipitates appeared to result from intramolecular or intermolecular reactions with the formation of strong covalent bonds rather than weak non-covalent bonds. The importance of disulphide bonding was excluded in the precipitation of both γG but not in the γM pyroglobulins. Heat precipitation of the monoclonal γM resulted in coprecipitation of other proteins, particularly γG globulin, which suggested a specific type of reaction with this immunoglobulin. The Interaction of the γM pyroglobulin, normal γG and heat produced an irreversible precipitate. [ABSTRACT FROM AUTHOR]

Thirty-one out of fifty patients receiving procaine amide were found to develop antinuclear antibodies belonging in most cases to the IgM and IgG classes and to a lesser extent to the IgA class. Specific interaction between these antibodies and a nucleoprotein component could be demonstrated in a large proportion of cases. No relation was found between occurrence of antinuclear antibodies and development of an immune response to procaine amide itself. [ABSTRACT FROM AUTHOR]

Immunochemical comparisons have been made of the F(ab')2 and the pFc' fragments of each of the four subclasses of human IgG. The F(ab')2 fragments of IgG 3 proteins were found to exhibit anomalous gel-filtration behaviour compared with similar fragments from the other subclasses. This difference was unrelated to carbohydrate content and may indicate a unique conformation for IgG 3 molecules. The pFc' fragments of all four subclasses were similar in size and antigenically indistinguishable by gel-diffusion tests but on both starch gel electrophoresis and immunoelectrophoresis the IgG 4 pFc' fragment was of faster mobility. Some minor products of pepsin digestion arising From the IgG 2, IgG 3 and IgG 4 subclasses were also investigated. These fragments were derived from the Fab regions of the respective parent molecules. [ABSTRACT FROM AUTHOR]

The techniques of starch gel electrophoresis, immunoelectrophoresis and high resolution gel filtration have been used to investigate the peptic cleavage or human G-Myeloma proteins of the four known subclasses. The appearance and fate of F(ab')2 and pFc' fragments and the persistence of undegraded IgG have been contrasted and distinctive patterns of pepsin sensitivity have been established for each subclass. The IgG 1 subclass is the most resistant and is degraded by pepsin in a manner which is closely similar to that observed for pooled IgG. IgG 2 molecules are also relatively resistant to peptic cleavage whereas IgG 3 and IgG 4 proteins are much more sensitive. Nevertheless all the subclasses are cleaved by the enzyme in similar susceptible regions and give rise at some stage to the same products: F(ab')2 fragment, pFc' fragment and peptides from the N-terminal half of the Fc region. [ABSTRACT FROM AUTHOR]

The electrophoretic distribution of Kappa and Lambda light chain antigenic determinants were studied in cerebrospinal fluid (CSF) and serum from cases with abnormal immunoglobulin G patterns on agar gel electrophoresis of CSF. Electrophoretically homogeneous immunoglobulin fractions containing an excess of either Kappa or Lambda determinants were found in CSF but not in serums. The findings indicate the production of monoclonal immunoglobulins within the central nervous system in multiple sclerosis. [ABSTRACT FROM AUTHOR]

By immunizing rabbits with immune precipitates containing autologous IgG as the antibody parts, most animals produced both rheumatoid factor-like antibodies and antibodies to human and rabbit F(ab')2 lgG. The latter antibodies resembled the human antibodies to the pepsin site of lgG by not reacting with untreated IgG and by reacting with immune precipitates made From autologous and homologous antibodies. The rabbit antibodies to the pepsin site of IgG in most cases consisted of a mixture of IgG and IgM, while the human antibody is usually pure IgG. The investigation demonstrated that in addition to rheumatoid factor, other human anti-lgG antibodies may also be due to antigenic stimulation by autologous IgG in immune complexes. [ABSTRACT FROM AUTHOR]

IgG, IgA, IgM and IgD concentrations in plasma were measured at three surveys of a rural Gambian community made over 13 months. 3523 samples were analysed. The pattern of change with age of mean levels of each immunoglobulin class was similar at each survey, although IgM levels were highest in the survey made at the end of the wet season. immunogiobulin levels in the same individual were found to be relatively stable in adults over the study period. Only minor correlations were found between the levels of different immunogiobulin classes in plasma from the same individual. Malarial parasitaemia was associated with increased mean IgG levels in age groups up to 20 years but with increased IgM levels only in the first 2 years of life. Plasma which contained precipitating antibodies to malarial antigens showed higher mean levels of IgG and IgM in most age groups. In association with splenomegaly mean IgG levels were increased throughout childhood while mean IgM levels were elevated only in the first 2 years. No consistent relationship between malaria and mean levels of IgA and IgD were noted. The only relationship found between haemoglobin concentration and immunoglobulin levels was a small negative correlation in respect of IgM. Clinical infection, other than malaria, was associated with increased mean levels of IgG and IgA in all age groups and of IgM in young children. Lower levels of IgG, IgA and IgM occurred in pregnancy; IgG levels seemed to fall progressively as pregnancy advanced. At certain ages mean levels of IgM and IgD were higher in females than males. [ABSTRACT FROM AUTHOR]

The IgG serum immunoglobulin fraction of two Burkitt's lymphoma (Mutua and Kiliopa) and one African nasopharyngeal carcinoma patient (Kipkoech) was conjugated to iodine-131 (131I) It is known from previous studies with fluorescein labelled conjugates that all three sera contain antibody against the Epstein-Barr virus (EBV)-associated membrane antigen complex, present on the surface, of lymphoblastoid cells in EBV-carrier cultures. All three radioiodinated conjugates attached to live cells of an EBV-carrying Burkitt line (Maku), but not to EBV-free Raji cells. A Swedish control serum (Berith) did not block the binding of any of the three conjugates, whereas unconjugated sera of Mutua, Kiliopa and Kipkoech showed various degrees of blocking and cross-blocking. The blocking patterns were in good agreement with previous tests, performed with the same sera against their fluorescein conjugated derivatives. Antibody release tests, involving preincubation of live cells with one of the three conjugates, followed by incubation with unlabelled serum revealed a certain 'hierarchy' between the three sera with regard to their ability to displace radioiodinated surface-coupled immunoglobulin. This ability could be related to the competitive behaviour of the same sera in the cross blocking tests. The results are believed to reflect differences in the affinity of the three antibodies, due either to differences in fit in relation to the surface antigen(s) carried by the Maku target cell, or to differences in the duration of immunization in the three patients. [ABSTRACT FROM AUTHOR]

A mixed immunofluorescent staining method for the detection of immune complexes in the tissues is described. This method demonstrated the presence of IgG-rheumatoid factor and IgG-β1C complexes in synovial membrane from patients with rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

A new method was used to measure immunoglobulin and total Protein concentrations in nasal secretions of normal infants and infants with acute respiratory infections and with allergies. A measured quantity of inulin was added to the administered wash solution in order to determine the dilution of the nasal secretions washed from the infants, in normal infants IgA concentration was less than IgG concentration. In nasal secretions from infants with acute respiratory infections IgA concentration was higher and IgG concentration was lower than in secretions from normal infants. Nasal secretions were studied without the inulin marker in a larger group of normal infants arid in infants with acute respiratory infections, a family history of asthma, atopic dermatitis or asthma. Only relative concentrations of immunoglobulins and total protein can be determined from these studies. There was no difference between the group with a family history of asthma and the control group. IgA/IgG and IgG/TP ratios in asthmatics were not significantly different from those in normal subjects. IgG/TP was significantly lower in asthmatics than in normal infants. Infants with atopic dermatitis had a lower IgA/IgG ratio in their secretions than normal nonallergic controls. The possible implications of these findings to the development of the immune system and the pathogenesis of disease are discussed. [ABSTRACT FROM AUTHOR]

Clinical, serological and cellular studies were carried out in five cases of Walden- ström's macroglobulinaemia with cryoglobulinaemia of the mixed IgM-IgG type and extremely high serum levels of rheumatoid factor activity. Clinically, no joint involvement or other distinctive features were found in these patients, as compared with other cases of primary macroglobulinaemia without ant-γ-globulin activity. The isolation of the monoclonal IgM immunoglobulins, as well as absorption studies with IgG and immuocytological investigations demonstrated that the whole of the rheumatoid activity was associated with the Waldenström-type paraproteins. Such cases seem to represent instances of a rheumatoid factor monoclonal gammapathy, in fact a subgroup of Waldenström's macroglobulinaemia. in view of the presence of an IgM paraprotein possessing anti-IgG activity, synthesized by the lymphocytoid cells infiltrating the bone marrow. [ABSTRACT FROM AUTHOR]

Immunofluorescent microscopy studies of jejunal biopsies from ten patients with gluten-induced enteropathy are reported. Eight biopsies were examined before and five after..onset of gluten-free diet. Fluorescent antisera specifically reacting with IgA, IgG and IgM were applied, and accordingly the cells were differentiated and quantitated. The immunofluorescence microscopy revealed an increased amount of immunoglobulin-containing cells in both treated and untreated cases of sprue. The distribution of the immunoglobulin-containing cells within the three immunoglobulin classes was significantly altered as the proportion of IgM- and IgG- containing cells was elevated. [ABSTRACT FROM AUTHOR]

Anti-lymphocytic IgG (ALG) in moderate doses postponed the onset of spontaneous renal disease in (NZB × NZW)F1 hybrid (BW) mice decreasing their mortality. This result only occurred if antibody formation to the ALG was prevented by first rendering the mice tolerant to normal rabbit IgG (NRG), otherwise acceleration of renal disease occurred. This acceleration was particularly marked if γ-globulin, rather than a purified IgG preparation of ALG were used and was further enhanced by adult thymectomy. The development of antinuclear antibody was not delayed by ALG nor was the rise in the serum IgM levels. The effects of ALG are seriously modified by alterations in factors such as dosage used. preceding tolerance to the NRC, thymectomy and strain of mouse used [ABSTRACT FROM AUTHOR]

The 24-hr urinary excretion and clearances of IgA, IgG, siderophilin and albumin have been determined on specimens from twenty-one hospital patients, nine of whom had urinary tract infection. Patients with normal creatinine clearance and urinary tract infection had significantly increased urinary excretion and clearances of all four proteins, compared to patients with normal creatinine clearance and no urinary tract infection. IgM was found in the urine of five patients with urinary tract infection, and in three of these IgD was also present. There was no evidence that the presence of IgM and IgD in the urine of these patients was a direct result of infection. [ABSTRACT FROM AUTHOR]

The article presents a study, which describes a family study on macroglobulinaemia patients. In this study, serum electrophoresis and quantitative determination of serum immunoglobulin levels were performed in 353 relatives of twenty-three patients with macroglobulinaemia. Only the number of abnormalities, both quantitative and qualitative, found in the IgM class was higher than would be expected in the general population. Abnormalities also occurred in the IgG and IgA classes, but their number is not higher than expected, thus indicating that they are not associated with the disease in the propositus.

The article describes cases of autoantibodies to haemoglobin being produced in cattle infected with Corynebacterium pyogenes. The antibody in one of these animals has been characterized and found to be a transient IgM precipitating antibody. The reaction of the antibody with haemoglobins from other species has been tested and it has been found to react with all normal mammalian haemoglobins tested and bird haemoglobin but not fish haemoglobin. In the course of studies of IgG allotypes in cattle it was found that one of the antisera in use produced very strong precipitation lines with a few sera and when studying families to find if the IgG allotype was in fact genetically controlled it was found that the sera giving strong precipitation did not lit the hypothesis of a simple mode of inheritance.

The article presents information on Ig-allotype-anti-Ig-allotype reaction in rabbit skin. In rabbits, immunized against allotype specificities local dermal reactions were produced by intradermal injections of the appropriate allotype antigen. The reactions were characterized by redness of the skin, infiltration and oedema. The reactions initially appeared about 24 hr after the intradermal injections. The present study shows that small amounts of allotypic antigen injected intradermally into rabbits immunized with the antigen in question produce local reactions characterized by redness of the skin, oedema and infiltration. The dermal reactions that could be produced after five or seven subcutaneous immunizations appeared about 24 hr after the injection.

The article presents information on a study which describes immunoglobulin G antibody to parathyroid oxyphil cells in the serum of one of nine patients with idiopathic hypoparathyroidism. This serum also reacted with the chief cells of the parathyroid. A limited number of unfixed frozen sections were obtained from a small parathyroid adenoma from a female patient aged 42 years with hyperparathyroidism. Immediately after the removal of the adenoma from the patient, the tissue was rapidly frozen and the sections prepared.

The article describes the effect of anti-lymphocytic serum on the development of experimental thyroiditis in rats. Two- to 3-month-old male rats derived from a random bred Wistar strain were used for immunization. The auto-allergic thyroiditis produced in rats by the injection of rat thyroglobulin in complete adjuvant can be suppressed by the administration of the IgG immunoglobulin fraction of heterologous (horse) anti-lymphocytic serum (ALS-IgG). ALS-IgG also suppresses the formation of circulating antibodies against rat thyroglobulin.

The article reports the serum levels of the immunoglobulins IgG, IgA and IgM in twenty-four normal Caucasians, forty-two normal New Guinea natives and 142 natives with tropical splenomegaly syndrome. The mean levels of IgG and IgM were significantly elevated in all groups of natives. The highest levels of IgM occurred in natives with splenomegaly, with a wide range of values. There were no significant differences in the levels of IgA or IgM between two groups of natives with splenomegaly from different regions, but the difference in IgG between the two groups was significant at the 5% level.

The article informs that a Bence Joney protein with cryoglobulin properties has been isolated from the urine of a myeloma patient. The Benee Jones cryoglobulin was of type K and had a sedimentation coefficient of 3-5S at a concentration of 5 mg/ml. Until recently, all cryoglobulins were thought to be intact IgG or fgM immunoglobulins. Several reports of urinary proteins of low molecular weight with cryoglobulin properties, however, indicate that intact immunoglobulin molecules are not essential for cryoglobulin formation. In studying the urinary protein from a patient with myeloma, a protein fraction was isolated which was found to have the characteristic gelling properties of cryoglobulins with precipitation on cooling and the typical solubility properties of free light chains on heating.

The article reports that the serum complement levels were determined in seven patients with mixed cryoglobulinaemia. All seven patients had either no measurable or very low levels of C'2. C'50 haemolytic units were determined in three patients and were also found low, although less striking. The mechanism by which the blood of these patients became depleted of C'2 could not be determined. Six patients had C'2 levels which were below the sensitivity level of the methods and one patient had a level of 220 units. The total complement levels were determined in three patients.