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A 5-month-old child with hemophagocytic reticulosis is described. Investigations revealed a grossly defective PHA response of the patient's lymphocytes which improved with chemotherapy. Defective glucose oxidation by phagocytosing cells and low IgA levels were demonstrated at diagnosis and have persisted despite chemotherapy. HL-A typing and chromosome studies did not reveal maternal lymphocytes in the child's circulation. The patient was treated with vinblastine and prednisolone and remains well after 11 months of treatment.

IgA, IgG, and IgM concentrations were determined in sera from 100 patients under treatment for epilepsy for at least 6 months. Low IgA was found in 25% of adult sera and in an even larger percentage of sera from children. IgM concentrations were also low, whereas there was no significant difference in the IgG concentrations compared with normal sera. IgA values were normal in untreated patients but fell during treatment with phenytoin, in one patient from 1.5 to 0.2 mg/ml within 2 months. Low or undetectable salivary IgA was a common finding, especially in gingival hyperplasia.

Evidence is presented to indicate that proteolytic and perhaps other enzymes of the louse midgut, essential to the nutrition of the louse, perform molecular dissection on the antirickettsial antibodies present in the blood of a typhus-immune host that selectively destroys, along with other functions, the portion of the antibody that determines the only known function by which antirickettsial antibodies may operate in host defense mechanisms, namely, opsonization of rickettsiae for enhanced ingestion by professional phagocytes and subsequent destruction. The epidemiologic significance of these findings is discussed in relation to the progressive destruction of cells that produce digestive enzymes of the louse midgut that occurs with progressive rickettsial infection, and the possibility of a negative feedback mechanism in transmission is introduced. Speculations that involve evolutionary concepts of both convergent and divergent varieties with respect to rickettsiae, potentially operational in a system that consists of an obligate blood-sucking arthropod vector and a vertebrate host capable of adaptive responses to both vector and rickettsial agent, are presented.

Dog serum and colostral immunoglobulin A (IgA) and free secretory component from colostrum were isolated using affinity chromatography. Both serum and colostral IgA showed similar susceptibility to reduction with dithiothreitol, but only colostral IgA released the additional subunit, bound secretory component. This released secretory component was identical with free secretory component with respect to electrophoretic migration, isoelectric focusing point, and molecular weight, but lacked some antigenic determinants. The amino acid composition and the N-terminal sequence of canine free secretory component was similar to that reported for the cow.

The effect of levamisole (1-2,3,5,6-tetrahydro-6-imidazo[2,1-b]thiazole monohydrochloride) treatment on the course of a Corynebacterium pseudotuberculosis infection and the ability of either vaccinated or unvaccinated randomly bred mice to resist challenge were investigated. It was found that either a double treatment of levamisole administered with or without a sublethal inoculation of C. pseudotuberculosis or a single treatment of levamisole alone had a significant effect on the ability of mice to resist challenge with virulent C. pseudotuberculosis. This prolonged, enhanced nonspecific and specific resistance was associated with a quantitative reduction in the geometric mean serum immunoglobulin levels, with the immunoglobulin G2 and immunoglobulin A levels being more severely affected. As the enhanced nonspecific resistance to C. pseudotuberculosis was associated with depressed serum immunoglobulin levels in the mice pretreated with levamisole alone, it was suggested that the cell-mediated immunity may play a more important role than the humoral immunity in the resistance to C. pseudotuberculosis infection.

A man aged 38 years developed chronic liver disease with characteristics of both haemochromatosis and active chronic hepatitis. Two of his relatives were found to have selective IgA deficiency. It is suggested that this case provides evidence that haemochromatosis may initiate active chronic hepatitis in a genetically susceptible subject.

Serum levels of C4, C3, IgG, IgM and IgA were measured by immunodiffusion in age matched groups of 48 sporadically encountered patients with ankylosing spondylitis, 56 with rheumatoid arthritis and 52 normal controls. Mean levels of C4 and IgA were significantly elevated in the sera of patients with sporadic ankylosing spondylitis, in comparison to normal controls. Mean IgA levels were also significantly elevated in 11 HL-A 27 positive patients with familial spondylitis but no such elevation was found in the sera of their healthy first-degree relatives with and without HL-A 27. The results of these studies suggest that humoral immune mechanisms may be involved in the pathophysiology of ankylosing spondylitis.

The local immune system of children suffering protein-calorie malnutrition (PCM) was investigated by analyzing the amount of immunoglobulins in the nasal washing on admission, repeatedly during 84 days of hospital therapy, and on follow-up, one to two years later. Although measured concentrations of total protein, IgG, and albumin in nasal washings were reduced in children with PCM, only secretory IgA concentrations were significantly lower (P less than .01) in PCM compared to normal children. Mean secretory IgA concentrations were significantly reduced on admission through hospital day 70 and returned to near normal thereafter. At one to two years after hospital discharge, mean concentrations of secretory IgA in nasal secretions were within normal limits. The concentrations of secretory IgA in nasal washings were lowest at a time when serum IgA was markedly elevated; serum IgA concentrations fell to normal values during dietary treatment. The possible role of secretory IgA deficiency in PCM and infection is discussed.

An auto-immune origin was postulated previously for ulcerative colitis. The present results do not support this hypothesis. Crohn's disease has been compared to sarcoidosis and lymphogranuloma venereum. Crohn's disease may be a virus infection coming from the bowel content. The virus may multiply, for instance, inside the submucosal lymphocytes.

Gamma-Glutamyltranspeptidase activity of patients having an ascitic cirrhosis due to ethanol consumption is high (139 mU/ml) when the patient is still drinking at the time of the assay; it is lower when the patient had stopped drinking at least two months before the assay (49 mU/ml). On the other hand, in 10 patients out of the 11 who submitted to a second assay gamma-glutamyltranspeptidase decreases as soon as the patient abstains from alcohol. In 4 abstinent patients re-examined one year after the first measurement, the gamma-glutamyltranspeptidase activity had decreased to the reference values of Szasz. The half time of the return to normal has been estimated by extrapolation from the ethylic model at between 11 and 54 days. We conclude that the hyper gamma-glutamyltranspeptidase in cirrhotics is due to the ethanol impregnation and that repeated assays of the enzyme show whether the patient abstains from alcohol or not.

IgA protease is a proteolytic enzyme found in whole human saliva and in dental plaque that cleaves both secretory and myeloma IgA of human origin to yield intact Fabalpha and Fcalpha fragments. To determine which bacteria are capable of producing this enzyme, we have examined a variety of strains normally found in the human oral cavity and a number of streptococci of known Lancefield group serotype. Streptococci of groups A, B, C, D, F, G, H, M, and N, Streptococcus mutans, Streptococcus sanguis, Streptococcus mitior, Streptococcus salivarius, Streptococcus faecalis, Veillonella, Lactobacillus, Actinomyces, Propionibacterium, Bacteroides, and Fusobacterium were grown in liquid medium, and fluids were examined for IgA protease activity. Only S. sanguis and clinically isolated group H streptococci elaborated IgA protease under the culture conditions used. Negative strains could not be stimulated to produce the enzyme when cultured in the presence of secretory IgA. Among the natural oral bacteria, capacity to produce IgA protease is restricted to certain species of Streptococcus, notably those of the group H serotype. Since secretory immunity is mediated by the IgA class of antibody, the presence of this enzyme at mucosal surfaces could modify the secretory immune function.

During a period commencing at birth and lasting for up to 27 months 193 milk samples have been collected from 29 mothers. The IgA globulin content was high immediately after birth, averaging 2.7 arb.U, decreasing to 0.3 arb.U within the first 2 to 3 weeks after birth, then remaining almost constant for the rest of the lactational period. In the case of IgG globulin, similar results were obtained, but the quantity was much smaller. IgM globulin was demonstrated in small quantities during the first 3 weeks of lactation. The lysozyme content varied considerably during the whole lactational period. Individual variations were found for all the immunoglobulins, while the concentration in the individual woman varied only slightly from day to day following in other respects the pattern described above. In 19 mothers IgA, IgG, IgM, lysozyme and electrolyte content were determined in serum and in milk from the right and the left breast on the same day. No difference in content was found between milk from the left and the right mammary gland. A positive correlation was found between the concentrations of IgA and sodium chloride in milk, between those of IgG in milk and serum, and between those of lysozyme in milk and serum. No variations were registered during the individual breast feeding, nor for the 24-hour period as a whole.

A routine program for evaluation of the protein pattern in serum and synovial fluid has been tested on 25 patients in a consecutive study. The program comprised agar gel electrophoresis, total protein and albumin determination, and immunochemical determination of antitrypsin, orosomucoid, haptoglobin, IgR, and IgA. Linear correlation analysis of corresponding data in serum and synovial fluid gave r-values for the five latter components which varied from 0.74 to 0.87. On this basis reference intervals in synovial fluid could be established. Total protein, haptoglobin and IgG were elevated in rheumatoid arthritis, compared with osteoarthritis.

We measured immunoglobulins in the sera of 33 patients on days 1, 3, 6, 10, and 17 and three to four weeks after surgical operations (mostly hysterectomy or appendectomy) or (six patients) after spinal injury. In the absence of infection or blood transfusion, IgG usually decreased slightly and transiently after hysterectomy or appendectomy, as did IgA or IgM after hysterectomy. IgD concentrations showed no consistent changes, but in one patient after hysterectomy and with minimal infection IgD concentration decreased sharply, which contrasted with significant and early increases in IgG, IgA, and IgM. IgD concentration was not correlated with type of operation, presence of infection, or changes in the other immunoglobulins. IgE concentrations either die not change or, in some patients, increased or decreased initially, after operation. We conclude that immunoglobulin concentrations in serum are subject to multiple, unpredictable influences after trauma.

The gonococcus and meningococcus, which infect human mucosal surfaces, elaborate a highly specific proteolytic enzyme which cleaves the immunoglobulin A1 subclass of the principal mucosal antibody, immunoglobulin A (IgA). The susceptible Pro-Thr bond lies in a unique region of the IgA heavy chain; the IgA2 subclass, lacking this peptide bond, is enzyme resistant.

We examined 20 corneas of ten subjects to determine the amounts and distribution of immunoglobulins and albumin. Immunoglobulins IgG and IgA were found in all corneas, were at the same level centrally and peripherally, and were at one-half and one-fifth the serum levels respectively. The amount of cornea IgG correlated with serum IgG, but not with IgA. Immunoglobulin IgM was present in five of the ten sets of eyes. No IgM was detected in the central buttons of four of the five sets where IgM occurred in the corneal periphery. Albumin was present in all corneas, but less centrally than peripherally. The cornea contains high levels of antibody proteins.

Separately collected parotid and submaxillary salivary samples from 20 diabetic and 20 matched control subjects were analyzed for flow rate, electrolyte content and immunoglobulin (IgA, IgG and IgM) levels. Flow rates did not vary significantly between the two groups of subjects; calcium ion content, however, was higher in the diabetic subjects for both salivary glands. The presence of salivary IgI in 6 of 10 patients was also a significant finding. Any attempt to draw a conclusion between the severity of periodontal disease and Diabetes Mellitus from the above findings is still speculative but does indicate further areas of research.

Intact human erythrocytes were cross-linked with glutaraldehyde (GA) or dimethyladipimidate (DMA) and tested for their ability to bind [125I]-IgG anti-Rh0(D) and to undergo antibody-mediated hemagglutination. There was no decrease in antibody binding after treatment with GA concentrations up to 1.25% and DMA concentrations up to 1%. Red cells treated with these concentrations of GA and DMA did not agglutinate. The techniques employed to induce agglutination of the cross-linked red cells involved "incomplete" IgG anti-Rho (D) in albumin, "complete" IgM anti-D Rho (D) in saline, and the antiglobulin (Coombs) reaction. The agglutinability of the chemically modified red cells was inversely correlated with the extent of fixation. The dissociation of antibody binding from agglutinability in cross-linked erythrocytes suggests that Rho (D) antigen mobility is required for red cell agglutination. Antigen mobility was manifested by the transition from a relatively monodisperse distribution pattern of Rho (D) antigen sites to one of large aggregates or clusters when agglutination was induced by IgM anti-Rho (D), IgG anti-Rho (D) agglutination of protease modified red cells, and by anti-IgG agglutination of IgG anti-Rho (D)-coated red cells. Antigen clustering was not as prominent in red cells agglutinated by IgG anti-Rho (D) in the presence of albumin. Even though antigen mobility is a prerequisite for antibody-mediated hemagglutination, clustering does not appear to be an absolute requirement. The degree of antigen clustering differs with varying types of agglutination.