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The aim of this study was to investigate neonatal Fc receptor (FcRn) concentration developmental pharmacology in adult and pediatric subjects using minimal physiologically-based pharmacokinetic (mPBPK) modelling. Three types of pharmacokinetic (PK) data for three agents (endogenous/exogenous native IgG, bevacizumab and palivizumab) were used. The adult group contained six subjects with weights from 50 to 100 kg. For pediatric subjects, seven age groups were assumed, with five subjects each having the weight of 95%, 75%, 50%, 25% and 5% percentile of the population. A first evidence-based rating system to evaluate the quality of the source data used to derive pediatric-specific mPBPK model parameter was proposed. A stepwise approach was used to examine the best combination of age/weight effect on the parameters of the mPBPK model in adult and pediatric subjects. IgG synthesis rate (K(syn)), extravasation rate (ER) and FcRn were fitted simultaneously to the PK of bevacizumab and native-IgG in both adult and pediatric. All fitting showed good fits based on the graphs and the coefficient of variation of the fitted parameters (

Practically, IgG charge can contribute significantly to thermodynamic nonideality, and hence to solubility and viscosity. Biologically, IgG charge isomers exhibit differences in clearance and potency. It has been known since the 1930s that all immunoglobulins carry a weak negative charge in physiological solvents. However, there has been no systematic exploration of this fundamental property. Accurate charge measurements have been made using membrane confined electrophoresis in two solvents (pH 5.0 and pH 7.4) on a panel of twelve mAb IgGs, as well as their F(ab&rsquo, )2 and Fc fragments. The following observations were made at pH 5.0: (1) the measured charge differs from the calculated charge by ~40 for the intact IgGs, and by ~20 for the Fcs, (2) the intact IgG charge depends on both Fv and Fc sequences, but does not equal the sum of the F(ab)&rsquo, 2 and Fc charge, (3) the Fc charge is consistent within a class. In phosphate buffered saline, pH 7.4: (1) the intact IgG charges ranged from 0 to &minus, 13, (2) the F(ab&rsquo, )2 fragments are nearly neutral for IgG1s and IgG2s, and about &minus, 5 for some of the IgG4s, (3) all Fc fragments are weakly anionic, with IgG1 &lt, IgG2 &lt, IgG4, (4) the charge on the intact IgGs does not equal the sum of the F(ab&rsquo, )2 and Fc charge. In no case is the calculated charge, based solely on H+ binding, remotely close to the measured charge. Some mAbs carried a charge in physiological salt that was outside the range observed for serum-purified human poly IgG. To best match physiological properties, a therapeutic mAb should have a measured charge that falls within the range observed for serum-derived human IgGs. A thermodynamically rigorous, concentration-dependent protein&ndash, protein interaction parameter is introduced. Based on readily measured properties, interaction curves may be generated to aid in the selection of proteins and solvent conditions. Example curves are provided.

Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits (PGNMID) is a newly identified and rare form of glomerulonephritis which is characterized by endocapillary proliferative or membranoproliferative with monoclonal deposit stain for IgG and a single light chain. We describe the case of a 63-year-old woman with type 2 diabetes who was considered to have PGNMID.

Glomerulopathy due to dysproteinemia can have a wide spectrum of pathologic and clinical features based on specific characteristics of the abnormal protein and the response induced within the parenchymal tissue. Monoclonal immunoglobulin G (IgG) deposition can manifest as a different glomerular disease. Proliferative glomerulonephritis (GN) with monoclonal IgG deposits (PGNMID) is a unique entity mimicking immune complex GN that does not conform to any of those subtypes. IgG monoclonal granular deposition in the glomeruli with a pattern similar to immune complex disease suggested by C3 and C1q deposition should prompt consideration of PGNMID. Literature is scarce in terms of recurrence of disease in renal allografts. In this article we present the clinical-pathologic features of three cases of PGNMID in the renal allograft showing the variable course and manifestation of the disease.

Proliferative glomerulonephritis occurring as a consequence of monoclonal glomerular deposits of IgG is uncommon. It is a form of renal involvement in monoclonal gammopathy that mimics immune complex glomerulonephritis. Here, we report the first series of proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) from the Indian subcontinent highlighting use of light chain immunofluorescence (IF) in routine renal biopsy interpretation. We retrieved 6 patients diagnosed as proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) out of 160 biopsies (3.7%) with membranoproliferative patterns over 5 1/2 years (2009–2014), one of whom had recurrence 6 months post-renal transplant. Four (67%) patients presented with rapidly progressive renal failure and two (33%) with nephrotic syndrome. None of these patients had overt multiple myeloma. The predominant histologic pattern was membranoproliferative with all the biopsies showing IgG3 Kappa deposits on IF. The deposits were primarily subendothelial on electron microscopy.

International audience; Le STUDIUM conference was held November 24-25, 2016 in Tours, France as a satellite workshop of the 5(th) meeting of the French GDR 3545 on "G Protein-Coupled Receptors (GPCRs) - From Physiology to Drugs", which was held in Tours during November 22-24, 2016. The conference gathered speakers from academia and industry considered to be world leaders in the molecular pharmacology and signaling of GPCRs, with a particular interest in the development of therapeutic GPCR antibodies (Abs). The main topics were new advances and challenges in the development of antibodies targeting GPCRs and their potential applications to the study of the structure and function of GPCRs, as well as their implication in physiology and pathophysiology. The conference included two sessions, with the first dedicated to the recent advances in methodological strategies used for GPCR immunization using thermo-stabilized and purified GPCRs, and the development of various formats of Abs such as monoclonal IgG, single-chain variable fragments and nanobodies (Nbs) by in vitro and in silico approaches. The second session focused on GPCR Nbs as a "hot" field of research on GPCRs. This session started with discussion of the pioneering Nbs developed against GPCRs and their application to structural studies, then transitioned to talks on original ex vivo and in vivo studies on GPCR-selective Nbs showing promising therapeutic applications of Nbs in important physiological systems, such as the central nervous and the immune systems, as well as in cancer. The conference ended with the consensus that Abs and especially Nbs are opening a new era of research on GPCR structure, pharmacology and pathophysiology.

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a recently described entity. It is featured by glomerular nonorganized monoclonal immunoglobulin G deposits. Monoclonal IgG deposits are associated with glomerular proliferative lesions, mimicking different types of immune-complex glomerulonephritis. We report two classic cases of PGNMID which fulfilled all criteria of this disease. We conclude that recognition of proliferative glomerulonephritis with monoclonal IgG deposits requires routine immunostaining for light chain and IgG isotype.

Proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID) is a rare and recently identified disease with a poor prognosis irrespective of the treatment. Recently, the possibility of recurrent or de novo PGNMID after kidney transplantation has been reported, which is associated with a better prognosis compared to PGNMID on native kidneys. Nevertheless, at present, due to the very few cases of recurrent PGNMID diagnosed, there is no proven effective treatment. Here, we report a case of recurrent PGNMID successfully treated with plasmapheresis, steroids and mycophenolate mofetil. Our report suggests that plasmapheresis might be a valid therapeutic option to treat recurrent PGNMID.

Membranous-like glomerulopathy with masked IgG-κ deposits (MGMID) is a novel entity requiring antigen retrieval on formalin-fixed paraffin-embedded tissue to detect the immunoglobulin by immunofluorescence. MGMID is clinically distinct from other glomerulopathies with non-organized monoclonal IgG deposits, although the source of the kappa-restricted IgG is uncertain. Careful examination including ultrastructural analysis is essential for identifying diseases such as MGMID that may be misclassified by routine methods and ultimately require alternative techniques for accurate diagnosis.

We report a 5-month-old Amish girl with atypical recombinase-activating gene (RAG)-deficient severe combined immunodeficiency disease. There was a lys992glu RAG-1 substitution leading to impaired RAG activity. Immunological studies revealed mildly decreased CD3+ T cells, markedly decreased CD4+ T cells, and oligoclonal T-cell receptor-Vβ T cells. B cells were markedly decreased but serum immunoglobulin levels were normal with monoclonal IgG and IgM antibodies.

First description of a case of early myeloma with monoclonal IgG, type kappa, anomaly plus Bence-Jones proteinuria and Fanconi's syndrome in a 67-year-old woman. Characteristic crystalline inclusion bodies were found in plasma cells of bone marrow and renal tissue.

A panel of four natural human monoclonal IgG antibodies derived from B lymphocytes isolated from regional draining lymph nodes of cancer patients has been developed and characterized. The four human antibodies are termed, RM1, RM2, RM3, and RM4. The immunoreactivity of this panel of four human antibodies is restricted to tumor cells. Individually, these human MAbs show tumor targeting and are effective in inhibiting tumor growth in nude mouse xenograft models. When used in combination the antibodies show an additive effect in slowing down the progression of tumors in xenograft models suggesting that cocktails of antibodies may be useful in the clinic.

An IgG mouse monoclonal antibody (10F05) against polyethylene glycol has been generated. The antibody reacts with PEG regardless of the linker used for PEG attachment, and is able to recognize a PEGylated peptide in plasma at concentrations as low as 3 pg/mL. The antibody is readily purified in substantial quantities. The PEG IgG will find significant utility in the sensitive detection of PEG derivitives during the pharmacokinetic characterization of PEGylated compounds.

Clostridium difficile infection has emerged as a growing worldwide health problem. The colitis of Clostridium difficile infection results from the synergistic action of C. difficile secreted toxins A and B upon the colon mucosa. A human monoclonal IgG anti-toxin has demonstrated the ability in combination therapy to reduce mortality in C. difficile challenged hamsters. This antibody is currently in a clinical trial for the treatment of human Clostridium difficile infection. More than one group of investigators has considered using polyclonal bovine colostral antibodies to toxins A and B as an oral passive immunization. A significant proportion of the healthy human population possesses polyclonal antibodies to the Clostridium difficile toxins. We have demonstrated that polyclonal IgA derived from the pooled plasma of healthy donors possesses specificity to toxins A and B and can neutralize these toxins in a cell-based assay. This suggests that secretory IgA prepared from such pooled plasma IgA may be able to be used as an oral treatment for Clostridium difficile infection.

We show that the natural autoantibody activity of amniotic IgG dramatically increases after purification, and that the IgG-depleted fraction can suppress the activity of IgG natural antibodies from amniotic fluid or from the maternal serum. This suppression is also observed towards serum IgG from unrelated adults but does not impair the tetanus antitoxin activity of serum-derived IgG. Absorption experiments and immunoglobulin separation by gel permeation demonstrate that this suppression is due to monomeric immunoglobulins of the IgA isotype. The inhibition is associated with an anti-F(ab')2 activity of the amniotic IgA, involving hypervariable regions of the IgG as demonstrated by different reactivities towards monoclonal IgG sharing the same family of VH and Vkappa domains. These results indicate that the inhibition of natural autoantibodies not only occurs with fetal and adult serum IgM, as reported by other groups, but also with amniotic IgA, suggesting a general and important phenomenon. In the case of the amniotic fluid, IgA could protect the fetus against maternal IgG autoantibodies without interfering with simultaneously translocated antigen-induced IgG antibodies to pathogens.

A residual IgG line is frequently observed inside the monoclonal IgG line on immunoelectrophoresis of IgG myeloma serum in reaction with anti-whole human serum. We found that the residual IgG line was observed exclusively in serum from IgG-λ type M-proteinemia when a goat antiserum to whole human serum was employed. However, with a horse antiserum to whole human serum, the residual IgG line was observed in sera from both the IgG-λ and κ type M-proteinemias. These phenomena led us to an idea that the appearance of the residual IgG line resulted from reaction with anti-κ or λ antibodies present in the anti-whole human serum antisera. Investigations of sera from a number of IgG M-proteinemia by anti-κ and λ antisera, and absorption tests with partially purified BJP of both types indicated that the occurrence of the residual IgG line is due to the reaction of polyclonal IgG with anti-κ or λ chain antibody present in the anti-whole human serum.

Submitted by Dulce Barreto (mdulce.barreto@chlc.min-saude.pt) on 2012-11-26T14:55:25Z No. of bitstreams: 1 Clin Immunol 2012_133.pdf: 193143 bytes, checksum: 70c91e8bb5f95f48e0cdd5c7c6de7a77 (MD5) Made available in DSpace on 2012-11-26T14:55:25Z (GMT). No. of bitstreams: 1 Clin Immunol 2012_133.pdf: 193143 bytes, checksum: 70c91e8bb5f95f48e0cdd5c7c6de7a77 (MD5) Previous issue date: 2012

The prevalence of peripheral blood B cells secreting antibodies reacting with the F(ab')2 fragment of monoclonal IgG was studied in five patients with multiple myeloma (MM), nine patients with monoclonal gammopathy of undetermined significance (MGUS) and six healthy controls. An enzyme-linked immunospot assay allowed direct visualization of antibody producing B cells. All patients had B cells producing antibodies to autologous or allogeneic monoclonal IgG. Autoreactive cells were found more frequently than alloreactive cells in seven out of nine patients with MGUS and three out of four patients with MM. The same frequency of alloreactive cells in the patient groups was detected in healthy individuals. These findings show the existence of B cells producing anti-idiotypic antibodies which could be a part of an idiotypic network in monoclonal gammopathies.

Monoclonal IgG rheumatoid factors (RFs) are identified using a novel immunoblot assay which detects RFs that bind to SDS-denatured Fc on nitrocellulose. Recognition of these self-associating antibodies is by the use of F(ab′) 2 fragments of light chain-specific antisera. In this way, IgG RFs can be easily identified and the precise binding characteristics to different isotypes of IgG, or other antigens, further specified. The assay can also be used to detect other classes of RFs such as IgM RFs. Although less sensitive than the standard ELISA, the use of this immunoblot RF assay (IRFA) will identify IgG RFs and their target antigen with precision.

Summary Cholinergic urticaria is one of the more common physical urticarias. Although it is often fairly mild, severe treatment-resistant disease may occur, with significant associated disability. Omalizumab, a monoclonal IgG anti-IgE antibody licensed for use in severe asthma, has recently been used successfully in several types of urticaria, including in one case of cholinergic urticaria. This paper reports a patient with severe cholinergic urticaria, unresponsive to antihistamines and multiple other treatments, whose disease was also unresponsive to omalizumab.

Streptococcus mutans is known to be a prime etiologic agent for the initiation and progression of human dental caries. Rapid, accurate, and quantitative detection of S. mutans will help us better understand the pathogenic mechanisms of dental caries and will help to develop methods for caries diagnosis and risk assessment. This study describes the development of three highly species-specific monoclonal IgG antibodies against S. mutans. The antibodies were used to develop a number of methods that quantitatively detect S. mutans in less

A new technique, liquid-liquid partition chromatography in an aqueous polyethylene glycol-dextran two-phase system, was used to detect differences in surface properties of antibodies with different antigen-binding sites. Employing well-characterized monoclonal IgG antibodies and Fab and Fc fragments thereof as well as chimeric IgG antibodies we found a remarkable relationship between structure of the antibody combining site and chromatographic behaviour. The surface properties of the IgG antibodies were dominated by those of its antigen-binding regions. In addition, our results indicated that the constant parts of the IgGs form similar scaffoldings, on to which CDRs of variable shapes and sizes are interspaced and constitute the major dominant differences in exposed surface properties.

We report the case of a woman, who initially presented with an IgG kappa-type monoclonal gammopathy. An IgD-secreting myeloma was diagnosed 2 years later. The patient died of severe renal failure and infection. The discrepancy between the immunoglobulin concentration estimated from the electrophoresis pattern and the immunonephelometric measurement of IgG, IgA and IgM led us to investigate the existence of an IgD myeloma. It was of the IgD kappa type and had electrophoretic characteristics identical to the initial monoclonal IgG. A common clonal origin for these two immunoglobulins is discussed.

Primary orthostatic tremor is of unknown aetiology and is believed to be a distinct entity rather than a subtype of essential tremor. We describe the first patient with a typical phenotype of primary orthostatic tremor who has a persistent isolated monoclonal immunoglobulin G band in the cerebrospinal fluid.

We evaluated the clinical characteristics and electromyographic features of 39 patients with monoclonal gammopathy of undetermined significance (MGUS) and neuropathy. Twenty-three patients had a monoclonal IgM protein, 13 had an IgG, and three had an IgA. In 15 patients of the IgM group, the M protein reacted with myelin-associated glycoprotein (MAG). Comparing IgM-MGUS and IgG-MGUS neuropathies, we found the following differences: (1) There was a statistically significant higher frequency of sensory loss in the IgM group. (2) Nine attributes of nerve conduction abnormality were statistically worse in the IgM group, with slowing of conduction velocities and prolonged distal latencies. (3) The frequency of monoclonal IgM was overrepresented in the MGUS neuropathy group. In general, the clinical and electrophysiologic features of the IgM-MGUS MAG-reactive group were not significantly different than the MAG-nonreactive group. Our cases are similar to those previously reported and suggest that monoclonal IgM-MGUS should be separated conceptually from monoclonal IgG neuropathies.

Monoclonal IgG components were found in the serum of 5 of 40 patients with chronic myelocytic leukemia (12.5%), as well as in 2 of 15 patients with acute myelocytic leukemia (13.3%). These findings may represent an involvement of the lymphoplasmacytic system in myeloproliferative disorders. The significance of this association is discussed.

The monoclonal IgM-κ and IgA-κ proteins from the serum of patient CM were initially shown to share identical idiotypic determinants (Fair et al., 1976). It was also shown that a portion of the IgG fraction from this patient's serum also contained the reacting idiotypic component. In this report we describe the purification to homogeneity of the IgG monoclonal protein from a later serum sample and show that this isolated IgG monoclonal protein shares identical idiotypic determinants with both the monoclonal IgM and IgA proteins. Our conclusions were based on four separate double antibody competitive equilibrium radioimmunoassays. Sequential changes in the levels of both IgG and IgA over a period of 75 months indicated that these two paraproteins fluctuated in parallel to one another during this period of time and were not significantly influenced by Chlorambucil therapy. Previous immunofluorescent data and the establishment of the structural identities of IgG to IgM and IgA suggest that both pathways of immunoglobulin differentiation (i.e. IgM → IgA and IgM → IgG) may be occurring in patient CM. The differences in the expression of these classes of immunoglobulin observed over the 75-month period may reflect the gradual maturation of these developmental pathways of antibody forming cells.

This is the first reported of a patient with hemarthrosis due to invasion of the synovial membrane by myeloma cells. With angiographic studies of the affected joint it was apparent that the tumor tissue extended from the destructive bone lesion of the femoral condyle into the synovial membrane. Intraarticular spontaneous bleeding was the first manifestation of a monoclonal IgG multiple myeloma; the hemarthrosis recurred after drainage but was controlled with local roentgen therapy.

A method for determining the affinity and the concentration of mouse monoclonal antibodies against human IgG has been developed. The method comprises two steps. First, monoclonal antibodies are allowed to combine with radioiodinated human IgG. Secondly, mouse monoclonal IgG with and without complexed IgG is precipitated with rabbit IgG against mouse IgG. As the antigen is divalent complexes of varying composition are formed in this system leading to deviations from linearity in plots obtained in commonly employed analytical systems. The theoretical background of these systems has been studied by computer simulation, and a concentration effect on the formation of immune complexes was demonstrated. The affinities (in terms of the association constants) of 6 monoclonal antibodies were estimated and found to be in the range from 2 × 106 M−1 to 5 × 108 M−1.

There is paucity of information regarding the prolonged plasma thrombin time known to occur in some patients with systemic lupus erythematosus. Detailed investigations of plasma from two such patients disclosed that IgG accounted for this defect in each case. IgG isolated from plasma of either patient possessed the property of delaying fibrin aggregation and prolonging the clotting times of fibrinogen. Preincubation of IgG from either patient with anti-IgG or anti-Fab (rabbit) serum abolished this anticoagulant property. Moreover, the anticoagulant IgG from the first patient was neutralized with anit-k chain and anti-IgG3, that from the second patient with anti-lambda chain and anti-IgG1 serum. These anticoagulants were also dissimilar with respect to their interactions with fibrin(ogen). IgG from the first patient had no anticoagulant activity against fibrin(ogen) species lacking intact Aalpha chains. IgG from the second patient displayed undiminished anticoagulant effect on such fibrin(ogen) species. We conclude that each anticoagulant interacted with a distinct region(s) on the fibrinogen molecule and that these interactions affect or involve sites that participate in the fibrin self-assembly process.

An antiserum was developed with specificity for the VkIII subgroup, as evidenced by a precipitin reaction with reference protein Man. The antiserum reacted specifically with 4 of 26 monoclonal IgM, 3 of 57 monoclonal IgG, and 2 of 44 monoclonal IgA immunoglobulins. N-terminal amino acid sequence analysis was performed on kappa chains from 8 of these M-components. All were found to belong to the VKIII subgroup, and J of them had valine in position 2. This high frequency (37%) of valine in position 2 is discussed.

To determine quantitatively the number and avidity of receptors for the Fc portion of IgG on human platelets, we have measured the binding to platelets of human monomeric monoclonal IgG, and of small covalently crosslinked polymers of IgG1 labeled with 125I. The binding of labeled IgG1 monomers to platelets is too weak to permit quantitation. The binding of dimers or larger polymers of IgG1 is much more avid (greater at 4 degrees C than 37 degrees C), is readily reversible, and is saturable. The number of receptor sites ranges from 400 to 2000 per platelet and the mean equilibrium association constant (Ka) for the binding of dimers at 4 degrees C is 2.2 x 10(7) M-1 +/- 0.9 x 10(7) M- 1. The binding is specific for the Fc portion of IgG, and IgG1 and IgG3 bind to the receptors much more avidly than IgG2 or IgG4. Unlabeled IgG1 dimers are about 7--8-fold more potent in inhibiting binding than are IgG1 monomers, and larger polymers are even more potent than dimers. Thus, the Fc receptors on platelets bind human IgG1 with the same specificity and similar avidity as Fc receptors on polymorphonuclear leukocytes (PMNs), but PMNs have about 300-fold more receptors per unit of surface area than platelets.

Rabbit anti-idiotype antisera were prepared against four human myeloma proteins. These antisera demonstrated a capacity to bind the 125I-labeled autologous purified monoclonal IgG, but failed to demonstrate any binding to 125I-labeled normal IgG or to labeled myeloma IgG obtained from other myeloma patients. The anti-idiotypic antisera were used with 125I-labeled autologous myeloma IgG preparations and goat antirabbit IgG for specific radioimmunoassay with a sensitivity limit of 20 ng/ml. Little or no cross-reaction occurred between these anti-idiotypic antisera and normal IgG preparations or other myeloma IgG proteins.

A 57-year-old man with skin psoriasis and psoriatic arthropathy, in whom an IgG-K monoclonal immunoglobulin was identified, is reported. A 7-year follow-up did not disclose any evidence of malignancy. The significance of this unusual occurrence is described.

We report the association of monoclonal mu-heavy chain and a monoclonal IgG K paraprotein in a patient with systemic lupus erythematosus (SLE). This association and the apparently benign nature of this biclonal gammopathy has not been previously reported.

1.A comparison has been made of the relative ability of immunofixation and immunoelectrophoresis to identify monoclonal IgG, IgA and IgM in three sera with high concentration and in three sera with low concentration of these proteins. 2. Immunofixation identified the proteins unambiguously in all six sera examined, whereas immunoelectrophoresis gave ambiguous results in one of the sera with high protein concentration and in three of the sera with low protein concentration. The superiority of immunofixation resulted from its greater resolution. It was condluded that immunofixation is the preferred technique for the identification of monoclonal immunoglobulins. 3. The sensitivity of immunofixation was greater at 40 degrees C than at 10 degrees C or 25 degrees C.

A 78-year-old woman with a plasmocytoma of the vagina is described. The diagnosis monoclonal IgG kappa-producing plasma cell tumour was based on immunohistochemical studies. Careful screening for other localizations including immunofluorescence of the bone marrow aspirate and in methyl-methacrylate embedded bone marrow biopsy specimen, yielded no evidence in favour of a multiple myeloma. To our knowledge only 5 patients with plasmocytoma of the vagina were previously reported, but only in the present case extensive immunohistochemical studies of tumour, bone marrow and blood were performed.

A patient is described with a monoclonal immunoglobulin of the IgG class in the serum and no detectable IgM and IgA. Extensive immunological investigations showed the absence of B-lymphocytes in bone marrow and peripheral blood. Moreover, plasma cells were not present in the bone marrow. The monoclonal IgG was synthesized in the gastrointestinal tract. The cellular immune-status of the patient was synthesized in the gastrointestinal tract. The cellular immune-status of the patient was normal. Clinically the patient suffered from gastrointestinal and severe respiratory tract infections. It was concluded that the findings are consistent with the diagnosis congenital agammaglobulinaemia with concurrence of monoclonal IgG. It was postulated that the cell clone in the gastrointestinal tract resulted from an escape of a pre-B cell clone from the recongized arrest of pre-B cells in congenital agammaglobulinaemia.

A comparison of murine monoclonal IgG subclass antisera with rabbit polyclonal IgG subclass antisera restriction of the monoclonal antisera and further antigenic heterogeneity within the IgG subclasses of at least two antigenic variants of IgG1, two of IgG2, two of IgG3 and a third subtype of IgG4.

Murine IgG subclasses show different affinities when they react with protein A. The temperature of application of the sample to protein A-Sepharose markedly influences the interaction of certain antibodies with this specific adsorbent. Elution of weakly bound mouse IgG could be carried out by mild temperature changes instead of lowering the pH, and this should be advantageous with certain immunoglobulins that are labile under acidic conditions.