Occurrence of lymphocytotoxins in multi-case rheumatoid arthritis families: relation to HLA.

The presence of lymphocytotoxic antibodies (LCA) and their association with HLA haplotypes has been studied in 27 multi-case rheumatoid arthritis (RA) families (13 multiplex and 14 simplex) in Northern India. Of the total 59 RA patients, 69.4% had cytotoxins in their sera as compared with 2.5% of healthy controls. No differences were observed in the frequency of LCA in relation to sex and rheumatoid factor. LCA against B cells were significantly more predominant than those against T cells. Twenty families studied for correlation of HLA with LCA showed greater intensity of reaction with DR4+ haplotypes, particularly in simplex families. Similarly, the frequency of LCA among patients and unaffected parents was greater in simplex compared with multiplex families. Haplotype sharing with the patient was increased in the relatives positive for cytotoxins in these families. An immunogenetic contribution made by the affected parent and a common environmental stimulus may be responsible for the increased production of LCA in multi-case families with RA.     

The relation of serum immunoglobulin A and delayed hypersensitivity skin tests to serum immunoglobulin E levels.

Serum IgA and IgE levels were obtained in 706 patients, 294 of whom were also tested for cutaneous delayed hypersensitivity. The results do not support the concept that a deficiency of serum IgA or of T lymphocyte function underlies the elevated serum IgE levels observed in a majority of allergic patients.     

Biological grading of breast cancer using antibodies to proliferating cells and other markers.

Quantitation of immunohistochemical staining by image analysis was performed on 50 breast cancers stained with the monoclonal antibody Ki-67 to determine the growth fraction and its correlation with tumor grade. A high degree of correlation was shown. For each case the DNA ploidy was determined by quantitation of the DNA Feulgen stain by computerized microdensitometry. DNA content of breast tumor cells correlated to the histopathologic grade at which poorly differentiated tumors are more likely to be aneuploid. Quantitation of immunohistochemistry for estrogen and progesterone receptors had a high degree of correlation with the steroid binding assay, such as dextran-coated charcoal assay (DCCA), and were weakly correlated to histologic grade. In summary, our results indicated that quantitation of Ki-67-positive nuclear area and of DNA content by image analysis provides an objective method for assessing tumor cell growth fraction and DNA ploidy. Quantitation of steroid receptors by immunohistochemistry is a better and easier technique than those currently used to determine the best therapy for postmenopausal women. These methods can be performed on small frozen sections or needle aspirates in quantities that are insufficient for current steroid binding assays. Thus, this method is prognosticly useful even for patients with small breast lesions.     

Rapid method to detect rubella immunoglobulin M and immunoglobulin A antibodies.

Immunoglobulin (Ig) G was removed from serum specimens by precipitation with gamma chain-specific anti-human IgG of rabbit origin. The remaining rubella virus-specific IgM (and IgA) antibodies were then detected by the rubella hemagglutination-inhibition test. This procedure has proven to be as reliable as estimations carried out with IgM fractions separated on a sucrose density gradient.     

A family study of HLA antigens and other genetic markers in schizophrenia

HLA antigens and 19 other genetic marker systems were studied in 12 families containing 2 or more members diagnosed as schizophrenic. In contrast with previous reports we could exclude linkage between the disorder and HLA, and we found no evidence of linkage with Gm or Gc. The disagreement between our results and those of a previous study, which suggested linkage between HLA and schizophrenia, could not be explained on the basis of genetic heterogeneity within the disorder. The problems of performing a linkage study in the face of diagnostic uncertainty and an unknown mode of inheritance of the main trait are discussed, and the measures taken in attempts to overcome these difficulties are described. Despite present drawbacks, genetic marker studies hold future promise as a means of detecting major gene effects in schizophrenia and other familial psychiatric disorders.     

HLA and immunoglobulin polymorphisms in idiopathic dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is an idiopathic heart muscle disorder. The presence of circulating cardiac antibodies and the association with HLA-DR4 are consistent with autoimmune pathogenesis in a subset of patients. Sixty-eight DCM patients and 277 controls were typed for IgG heavy-chain constant region (Gm) and kappa light-chain (Km) allotypes. All patients and 210 of the 277 controls were HLA-DR typed. The Gm (1, 3, 17; 23; 5*, 21, 28) phenotype was overrepresented in DCM compared with controls (25% vs 13%, p = 0.0139, pc = NS, RR = 2.23). The frequency of this phenotype was higher in patients with younger age at onset, shorter symptom duration, and among those who were positive for cardiac as well as for non-organ-specific autoantibodies than in controls. A higher frequency of the Gm (1, +/- 2, 3, 17; +/- 23; 5*, 21, 28) heterozygous phenotypes was also found in DCM compared to controls (40.91% vs 26.89%; p = 0.02, pc = 0.04, RR = 1.88). The finding of Gm heterozygosity in DCM was associated with serum positivity for cardiac antibodies. A higher proportion of DCM patients were positive for both the Gm (1, 3, 17; 23; 5*, 21, 28) phenotype and HLA-DR4 compared to normals (3/68 vs 0/210; p = 0.04, RR = 22.50).(ABSTRACT TRUNCATED AT 250 WORDS)     

Do levels of immunoglobulin G antibodies to foods predict the development of immunoglobulin E antibodies to cat,dog and/or mite?

BACKGROUND: In children at high risk of inhalation allergy, food sensitization is associated with an increased risk for sensitization to inhalant allergens. Furthermore, this association was also found in a cross-sectional study. OBJECTIVE: To examine in a prospective study, whether levels of IgG to foods (i.e. mixture of wheat and rice, mixture of soy bean and peanut, egg white, cow's milk, meat, orange and potato) indicate an increased risk for the future development of IgE antibodies to inhalant allergens in a low-risk population and whether they can be used as predictors of the subsequent development of IgE antibodies in young, initially IgE-negative children. METHODS: Coughing children, aged 1-5, visiting their GPs, were tested for IgE antibodies to mite, dog and cat (RAST) and IgG (ELISA) to foods. All IgE-negative children were retested for IgE antibodies after two years. The IgG results (66 percentiles) of the first blood sample were compared to the RAST-scores of the second blood sample. RESULTS: After two years, 51 out of 397 (12.8%) originally IgE-negative children, had become IgE-positive for cat, dog and/or mite. An increased IgG antibody level to wheat-rice (OR = 2.2) and to orange (OR = 2.0) indicated an increased risk of developing IgE to cat, dog or mite allergens. In addition to IgG to a mixture of wheat-rice and orange; total IgE, breastfeeding, eczema as a baby and age were the most important predictors for the subsequent development of IgE to inhalant allergens. DISCUSSION: An increased IgG antibody level to a mixture of wheat-rice or orange, indicates an increased risk of developing IgE to cat, dog or mite allergens. This indicates that excessive activity of the mucosal immune system is present before IgE antibodies to airborne allergens can be demonstrated. Nevertheless, IgG to foods is not very helpful (with a positive predictive value of 16.5%, and negative predictive value of 90.6%) in identifying individual children at risk in clinical practice. However, besides other risk factors, IgG to wheat-rice and to orange could be useful as a screening test for studies in the early identification, i.e. before IgE antibodies can be detected, of children with an increased risk of developing IgE antibodies in the future.     

Interplay of immunoglobulin G heavy chain markers (Gm) and HLA in predisposing to systemic lupus nephritis

We have studied the distribution of IgG heavy chain markers (Gm) among 90 Hungarian patients with systemic lupus erythematosus (SLE) (55 of whom were also typed for HLA). This study confirms previously described increases in HLA-B8 and DR3 in this condition. No difference in the distribution of Gm phenotypes was found between patients and 168 controls from the same geographical area. HLA-B8/Gm homozygous individuals were, however, at greater risk for SLE (relative risk = 5.13) compared to B8 + Gm heterozygotes or B8- individuals, irrespective of Gm phenotype. When patients with renal manifestation (n = 40) were compared to those without, the Gm phenotype 3; 5, 13 was found to be significantly increased (chi 2 = 10.36, P less than 0.0001, relative risk (RR) = 4.69). HLA and Gm increased additively the risk for renal manifestations in that for those patients who were both Gm3;5,13+ and HLA-B8+, PR was 110, while it was 21.2 for Gm3;5, 13-/B8+, 7.9 for Gm3;5, 13+/B8- and 1.0 for Gm3;5, 13-/B8- patients. The study suggests that combined HLA and Gm typing can be used to identify SLE patients at high risk for manifesting renal abnormalities.     

Interference of Salivary immunoglobulin A antibodies and other salivary fractions with adherence of Streptococcus mutans to hydroxyapatite.

The adherence of Streptococcus mutans to hydroxyapatite was studied in the presence of salivary fractions with varying activity of naturally occurring immunoglobulin A (IgA) antibodies. Human parotid saliva from different donors was fractionated by chromatography and compared. Salivary IgA antibodies had no decisive effect on the adherence of the S. mutans strain used. High-molecular-weight salivary components from some subjects had an adherence-promoting effect, whereas fractions collected after the void volume of a Sepharose 2B column always inhibited adherence. The data indicate that the influence of unfractionated saliva on adherence is dependent on the net effect of adherence-promoting and adherence-inhibiting components. This principle has to be considered when the effect of human saliva on microbial adherence is studied.     

Diagnostic significance of immunoglobulin M antibodies to Toxoplasma gondii detected after separation of immunoglobulin M from immunoglobulin G antibodies.

Failure to demonstrate immunoglobulin M (IgM) antibodies by indirect immunofluorescence (IgM-IFA) in sera from some patients with acute acquired toxoplasmosis has recently been attributed to an inhibitory effect of high titers of IgG antibodies in these sera (Pyndiah et al. J. Clin. Microbiol. 9:170-174, 1979). To confirm these findings and define their importance for diagnosis, we used gel filtration to separate IgM from IgG antibodies in a series of sera that were negative in the IgM-IFA test. A total of 68 sera were from patients with acquired toxoplasmosis, 13 were from uninfected adults, 13 were from infants with congenital toxoplasmosis, and 7 were from uninfected neonates. Of the 68 sera from patients with acquired toxoplasmosis, IgM preparations (from the separated sera) were positive in the IgM-IFA test in 36 (53%). There was a significant (P = 0.00003) association between high titers of IgM-IFA antibodies in the IgM preparations (corrected for dilution of IgM antibodies by the gel filtration procedure) and recent acquisition of infection. IgM antibodies were also detected in 5 (38%) of the IgM preparations of 13 sera from congenitally infected infants but not in any of the IgM preparations of sera from uninfected neonates. IgG antibodies to Toxoplasma gondii were shown to interfere with demonstration of IgM antibodies in the IgM-IFA test. Treatment of sera with protein A resulted in greater dilution of IgM antibodies and less efficient separation of IgM from IgG antibodies than did separation of sera by gel filtration. Treatment of sera with protein A did not result in increased detection of IgM antibodies to T. gondii. Testing of IgM preparations (obtained by gel filtration) resulted in a significant increase in sensitivity of the IgM-IFA test for the diagnosis of recently acquired and congenital toxoplasmosis.     

Serum immunoglobulin changes in relation to tonsil and adenoid surgery.

In the course of clinical trials of tonsillectomy, adenoidectomy, and adenotonsillectomy, we measured serum levels of immunoglobulins G, A, and M by rate nephelometry in 268 subjects at baseline and at intervals after receipt or nonreceipt of surgery. Up to 30 months after baseline we observed a consistent pattern of change only in levels of immunoglobulin G, decreases in which tended to occur more commonly and be of greater magnitude in subjects who received tonsillectomy or adenotonsillectomy than in corresponding control subjects. However, in both surgical and control subjects the subsequent incidence of throat infection showed no relationship to either contemporaneous immunoglobulin levels or changes from baseline levels. A decline in serum immunoglobulins following tonsillectomy appears not to be a risk factor for developing throat infection, and may reflect a reduction in antigenic stimulation.     

Nerve-evoked secretion of immunoglobulin A in relation to other proteins by parotid glands in anaesthetized rat

Secretion of fluid and proteins by salivary cells is under the control of parasympathetic and sympathetic autonomic nerves. In a recent study we have shown that, in the rat submandibular gland, autonomic nerves can also increase the secretion of IgA, a product of plasma cells secreted into saliva as SIgA (IgA bound to Secretory Component, the cleaved poly-immunoglobulin receptor). The present study aimed to determine if parotid secretion of SIgA is increased by autonomic nerves and to compare SIgA secretion with other parotid proteins stored and secreted by acinar and ductal cells. Assay of IgA in saliva evoked by parasympathetic nerve stimulation immediately following an extended rest period under anaesthesia indicated that it had been secreted into intraductal saliva in the absence of stimulation during the rest period. The mean rate of unstimulated IgA secretion (2.77+/-0.28 microg min(-1) g(-1)) and the 2.5-fold increase in IgA secretion evoked by parasympathetic stimulation were similar to results found previously in the rat submandibular gland. Sympathetic nerve stimulation increased SIgA secretion 2.7-fold, much less than in the submandibular gland. SDS-PAGE and Western blot analysis with anti-IgA and anti-Secretory Component antibodies confirmed that SIgA was the predominant form of IgA in saliva. Acinar-derived amylase and ductal-derived tissue kallikrein were more profoundly increased by parasympathetic and particularly sympathetic stimulation than SIgA. Overall, the results of the present study indicate that SIgA forms a prominent component of unstimulated parotid salivary protein secretion and that its secretion is similarly increased by stimulation of either autonomic nerve supply. The secretion of other parotid salivary proteins that are synthesized and stored by acinar or ductal cells is upregulated to a much greater extent by parasympathetic and particularly sympathetic stimulation.     

Enzyme-linked immunosorbent assay for immunoglobulin G and immunoglobulin A antibodies to Shigella flexneri antigens.

An enzyme-linked immunosorbent assay has been developed to detect class-specific antibodies to Shigella flexneri lipopolysaccharide antigens. This enzyme-linked immunosorbent assay system has been used to measure antibodies present in serum or intestinal secretions without further purification. It is considerably more sensitive than passive hemagglutination, allowing detection of as little as 1.3 ng of specific immunoglobulin G antibody per ml in immune sera. Optimal conditions for this assay are outlined in this report.     

HLA markers in parents of triploid conceptuses.

Twenty-eight HLA-A and B markers have been tested in 49 couples who had one or more triploid abortions. The antigen frequencies were compared to those of 209 couples and 591 normal individuals as controls. No significant deviations were observed. However, a non significant excess of antigens shared in common by both parents was shown in comparison with the normal couples. This could be related to a possible dispermy mechanism. On the other hand, a slight excess of A 28 may be in relation to a possible anomaly of gametogenesis.     

Detection of immunoglobulin G antibodies to cholesterol in antisera to mycoplasmas.

Antisera were produced by inoculation of mycoplasma cells grown in PPLO broth supplemented with rabbit serum alone or rabbit serum plus Freund complete or incomplete adjuvant. By using an enzyme-linked immunosorbent assay, immunoglobulin G antibodies to cholesterol were detected in antisera to mycoplasmas (Mycoplasma salivarium ATCC 23064, M. orale ATCC 15539, M. buccale IID 802, M. faucium IID 996, and M. hominis IID 801) and rabbit serum.