Human leucocytic antigens (HLA) in breast cancer.

HLA frequencies of fifty (50) female breast cancer patients were compared with 200 age matched female controls. A total of 20 HLA-A locus, 35 HLA-B locus and 8 HLA-C locus antigens were studied. The HLA-A2, A11, Aw19 and A30; HLA-B8, B14 and HLA Cw6 were found significantly higher than the controls. The HLA-A11, HLA-Aw19 and HLA-B8 were found protective whereas, HLA-A2, HLA-B14 and HLA-Cw6 were a risk for breast cancer. The prective antigens' probable involvement through immunogenic mechanism in breast cancer is emphasized in this article.

Metabolic factors in the development of retinopathy of juvenile-onset type I diabetes mellitus.

Thirty-five patients of insulin-dependent diabetes mellitus (IDDM) were investigated for the effect of various metabolic factors on retinopathy. The severity of retinopathy increased with duration and age of onset of IDDM. Degree of glycaemia (fasting blood sugar, FBS) was similar in patients with or without retinopathy. All IDDM patients as a group showed severe carbohydrate intolerance with lower basal and post glucose serum immunoreactive insulin (IRI) levels and serum C-peptide radioimmunoreactivity (CPR) as compared to controls. The insulin secretory response was similar in no retinopathy, mild retinopathy and severe retinopathy groups. Patients with retinopathy had higher incidence of hyperlipidemia but mean serum levels of cholesterol and triglyceride were similar. This study does not suggest a direct relationship between the various metabolic factors studied and retinopathy due to IDDM.

Role of cell growth factor (interleukin-2) and its receptors in carcinoma cervix patients.

Host immunity plays an important role in neoplasia. Neoplastic activity is known to correspond with the disturbances in immunological mechanisms. T-lymphocytes DNA replication and mitosis are determined by a critical threshold of signals generated by the interaction between interleukin-2 (IL-2) and its receptors. So we planned to study the level of IL-2 in carcinoma cervix patients. Twenty healthy (normal) and fifty carcinoma cervix patients were investigated. The level of IL-2 was estimated by thymidine incorporation [Anderson et al., Eur. J. Immun. 9 (1979) 581-587]. A remarkable decrease in concentration of IL-2 in serum of the patients (mean = 21.62 U/100 microliters) when compared with normal healthy individuals (36.86 U/100 microliters). Immunotherapy in the form of IL-2 can be suggested in such patients.

HLA-B5 and B21 antigens in aortoarteritis.

The distribution of class I HLA antigens (HLA-A, B) were determined in 50 patients of Aortoarteritis in an Indian population. This included 29 females and 21 males. The difference in antigen frequency was observed between patients and controls with reference to HLA-A19, B5 and B21 antigens. A decreased frequency of HLA-A19 was observed in the patients as compared to controls (14% vs 33.25%, X2 = 6.81, P less than 0.025). Of the B locus antigens, an increased frequency of HLA B5 was observed in the patients as compared to controls (48% vs 29.5%, X2 = 6.2, P less than 0.025). HLA-B21 was also increased in the patients as compared to the controls (18% vs 6.5%, X2 = 6.67, P less than 0.025). These data suggest the involvement of genetic factor (s) in the aetiopathogenesis of this disease. Further, the observations indicate that HLA-B5 and B21 may be associated with Aortoarteritis.

HLA antigens in Asian Indian patients with Graves' disease.

A study of 57 Asian Indian patients with Graves' disease revealed a significant increase in the frequency of HLA-DQW2 (61.4%) as compared to the control population (22.6%) giving a relative risk of 5.4. Less prominent but statistically significant increase in the frequency of HLA-A10 (29.8% patients as opposed to 10.5% controls) and HLA-B8 (28.1% patients as opposed to 8.7% controls) was also observed. Further, patients carrying the phenotypes HLA-A10 and HLA-B8 were more prone to develop the disease at a younger age. Two HLA haplotypes, namely A10-B8 and B8-DR3, were found in significant linkage disequilibrium in our patients with Graves' disease. Patients carrying these haplotypes also had a tendency to develop the disease at an earlier age.

HLA antigens in Indian population with non-specific aortoarteritis.

HLA typing of Class I antigens (HLA - A & -B loci) was done for 65 patients suffering from nonspecific aortoarteritis, in Indian population. The diagnosis of these patients was based on clinical findings and confirmed by angiographic studies. Decreased phenotype frequency of HLA-A19 (p less than 0.005, relative risk 0.28), increased frequency of HLA-B5 (p less than 0.005, relative risk 2.46) and B21 (p less than 0.005, relative risk 3.25) was observed when compared with the control group. A decreased frequency of two other alleles of B locus i.e. B35 (p less than 0.005, relative risk 0.27) and B40 (p less than 0.05, relative risk 0.04) was seen in patient group as compared to control. The data indicate the possible association of HLA-B5 and B21 antigens with the nonspecific aortoarteritis.

HLA-DR/DQ antigens and reactivity to B cell alloantigen D8/17 in Indian patients with rheumatic heart disease.

D8/17, a B cell alloantigen, and its occurrence with DR/DQ antigens was examined in 54 patients with rheumatic heart disease and matched North Indian controls. Thirty-four patients (62.9%) carried D8/17 as compared with a frequency of 12.5% in controls (chi 2 by Yates', 18.75; p less than 0.0001). A marginally increased frequency of human leukocyte antigen (HLA)-DR3 (44.2% vs. 28.8%) and a significantly reduced frequency of HLA-DR2 (21.1% vs. 46.6%; p less than 0.005) was observed in patients as compared with controls. However, the most significant positive association was observed with HLA-DQw2 (63.4% in patients and 31.5% in controls; chi 2 by Yates', 9.85; p less than 0.005). The DQw2 association was significant only in the D8/17-positive patients. These observations suggest that the disease susceptibility gene in rheumatic heart disease may be nearer to the HLA-DQ locus than to the HLA-DR.

Genetic marker in juvenile diabetic retinopathy.

Thirty five patients with insulin dependent diabetes mellitus (IDDM) were investigated for development of retinal microangiopathy by fluorescein angiography. HLA typing (A,B.C antigens) was done as a genetic marker. There was no statistically significant difference in the frequency of HLA antigens between patients without retinopathy (Gr.I) and with retinopathy (Gr.II) Frequency of various HLA antigens did not differ significantly in the mild and severe retinopathy groups or in comparison with controls. HLA B8 was significantly over represented in the patients of IDDM as a single group (GrI + II) when compared with controls (26% vs 8%). HLA profile was not a predictor of either the development or the severity of retinopathy in IDDM.

Possible HLA influence in governing susceptibility to non-cirrhotic portal fibrosis.

Forty-eight unrelated North Indian patients with non-cirrhotic portal fibrosis were studied for the distribution of HLA-A, B and DR antigens. No significant differences were observed in the distribution of HLA-A and B locus antigens. In the DR locus, the frequency of DR3 was significantly increased in the patients as compared to the controls (71.7% vs 26.1%, X2 = 25.3), while HLA-DR2 was significantly reduced (X2 = 11.3). Another striking observation was the presence of DR7 in all males negative for HLA-DR3. The results suggest an autoimmune pathogenesis of the disease and that susceptibility to non-cirrhotic portal fibrosis may be HLA class II mediated, with HLA-DR3 influencing susceptibility and DR2 conferring protection. Other genetic factors are also involved.

HLA, blood groups and secretor status in patients with established rheumatic fever and rheumatic heart disease.

The distribution of HLA-A, -B and -DR antigens as well as blood groups and secretor status was studied in sporadic, North Indian patients of rheumatic fever and rheumatic heart disease. While HLA-Aw33 occurred with an increased frequency in the patient group (X2 = 4.01), no statistically significant differences were observed in the frequency of B-locus antigens. In the DR locus, HLA-DR3 was found to be significantly increased (50% vs 26.1%, X2 = 13.8) and DR2 significantly reduced (21.8% vs 47.0%, X2 = 15.6). Also, there was a preponderance of non-'O' blood group individuals in the patient group as compared to controls. The DR3 association was significant only in those patients of RHD who did not have any previous history of rheumatic fever. These results indicate that susceptibility to rheumatic heart disease is HLA-class II mediated, with HLA-DR3 influencing susceptibility and DR2 conferring protection.

Distribution of HLA antigens in a sample of the North Indian Hindu population.

The Indian population can be divided broadly into Dravidians and the Aryans. In this report, we have attempted to analyze the HLA genetic profile of 400 native North Indian Hindus of Aryan descent. The gene frequencies of a majority of class I and II antigens show similarity to the Caucasoid population. An interesting finding was a complete lack of antigen B14 while B16 and B41 occurred with the least frequency. Haplotype A10, B8 with significant positive linkage disequilibrium as well as showing the highest incidence is characteristic of North Indians.

HLA-DR antigen frequencies in a North Indian type I diabetic population.

Eighty-eight North Indian patients with type I, insulin-dependent diabetes mellitus (IDDM) and 113 unaffected individuals were typed for HLA-DR antigens from DR1 to DR7. The frequency of HLA-DR3 was significantly increased in the patients as compared with the controls (78.4% versus 25.7%, corrected P = 1.68 X 10(-12], the relative risk (RR) of 10.52 being much higher than that reported in the Western IDDM population. HLA-DR2 showed a significant negative association (RR = 0.18, corrected P = 1.03 X 10(-5], but DR4 had no relationship with IDDM in the present study (RR = 1.12, P = 0.12). These results emphasize the differences in HLA-IDDM associations among different ethnic groups.

Ankylosing spondylitis in North India: a clinical and immunogenetic study.

Fifty-one North Indian patients with ankylosing spondylitis (AS) are described with mean age of onset 21.2 years and male to female ratio of 16:1. AS began with peripheral arthritis in 47%, low back pain in 41%, acute anterior uveitis in 10%, and heel pain in 2% of the patients. 76% of 51 patients had one of the extra-axial features of AS: peripheral arthritis (61%), heel pain (24%), anterior uveitis (22%), urethritis (12%), kidney disease (10%), mucosal ulcerations (6%), aortic incompetence (4%), and apical pulmonary fibrosis (4%). A majority (71%) of the patients with peripheral arthritis had mono- or oligoarthritis affecting mainly the lower limb joints. Two patients had coexistent rheumatoid arthritis also. HLA-B27 antigen was detected in 48 (94%) of 51 patients compared with 7 (6%) of 118 controls (relative risk 254; Fisher's exact p = 3.49(-29]. On comparing patients with juvenile onset AS and patients with adult onset disease we found peripheral arthritis to be more frequent at the beginning and during the course of disease in the former.

HLA haplotype segregation study in multiple case families of pulmonary tuberculosis.

Twenty-five multiple case families of pulmonary tuberculosis were HLA typed and the data analysed by the lod score method. There was no evidence of linkage between the susceptibility gene and pulmonary TB, though there were consistently positive female scores. A number of other chromosome 6 genetic markers tested did not reveal any significant deviation in the patient group as compared to the controls, except GLO 2-1 which occurred with a significantly decreased frequency in the former.

HLA antigens in acute anterior uveitis and spondyloarthropathies in Asian Indians and their comparison with American whites and blacks.

HLA antigen frequencies in 53 unrelated Asian Indian patients with acute anterior uveitis, with or without associated spondyloarthropathies, were compared with our published data on American Whites and Blacks. The most frequent HLA phenotype among uveitis patients with associated ankylosing spondylitis was A9(W24), B27 in Asian Indians as compared to A2, B27 in the American Whites and Blacks.

Human leukocyte antigen (HLA)-linked control of susceptibility to pulmonary tuberculosis and association with HLA-DR types.

To demonstrate human leukocyte antigen (HLA)-linked control of susceptibility to pulmonary tuberculosis, 25 multiple-case families were tissue typed for class I and class II HLA specificities. Eight non-HLA genetic markers were also examined for any indication of other genetic factors that might influence the Mycobacterium tuberculosis infection. Observations on estimated HLA haplotype segregation in the sibs suggest that 84% of the affected sibs shared significantly more often than expected a common haplotype with each other than the normal unaffected sibs (P less than 0.001). Also, there was a skewed transmission of DR2 to diseased offspring from diseased parents (21 of 27) and to diseased offspring from healthy parents (15 of 17) in contrast to the transmission of DR2 from either group of parents to healthy offspring (six of 15 and 10 of 16, respectively). The segregation of non-HLA polymorphisms did not deviate significantly from the expected figures. These data provide strong evidence in favor of DR2-associated susceptibility to pulmonary tuberculosis.