Chlamydial antibody crossreactivity with peripheral blood mononuclear cells of patients with ankylosing spondylitis: the role of HLA B27.

We have previously reported the association of Chlamydia trachomatis with HLA B27+ related diseases. To investigate the possibility that chlamydial antibodies serve to localize the immune response in such diseases, we examined the crossreactivity of chlamydial antibodies (rabbit anti-D and anti-L2 serotypes) with peripheral blood mononuclear cells of patients with ankylosing spondylitis (AS) and anterior uveitis (AU) and with human and bovine ocular tissue and cells in culture. Our results indicate a significantly increased percentage binding of chlamydial antibody (D serotype) to the mononuclear cells of HLA B27+ patients with AS when compared with HLA B27- patients with AS (12.9% +/- 2.2 versus 5.4% +/- 2.2), B27+ controls (5.5% +/- 1.5) and B27- controls (6.1% +/- 1.0). There was no significant difference between controls and HLA B27+ patients with AU (6.6% +/- 1.9) and B27- patients with AU (8.7% +/- 1.1). This crossreactivity could not be blocked by monoclonal HLA B27 antibody. Chlamydial antibodies (D and L2) crossreact with human and bovine conjunctiva but not uvea, tissue culture derived iris fibroblasts or smooth muscle cells. Our results provide additional support for the concept of crossreactivity between antibodies to microbial agents and peripheral blood mononuclear cells of patients with HLA B27+ AS.     

Cell-mediated immune response to chlamydia in anterior uveitis: role of HLA B27

The relationship between HLA B27 anterior uveitis (AU) and evidence of chlamydia trachomatis infection was investigated in 35 consecutive patients attending a uveitis research clinic, using a complement fixation test and lymphocyte transformation test to chlamydia (ornithosis-psittacosis) group antigen. A significant stimulation index (SI greater than 2) was found in 73% (11/15) of the HLA B27 positive patients compared with the HLA B27 negative AU patients and controls (P less than 0.03). There was no difference between AU patients with and without associated rheumatic disease or in terms of antibody response. The results of the present study indicate a significant relationship between the cell-mediated immune response to chlamydia group antigen and the HLA B27 positive subgroup of patients with AU.     

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与胆石症

对４０例胆石症患者进行ＨＬＡ－Ａ、Ｂ、ＤＲ、ＤＱ抗原分型，发现患者组ＨＬＡ－Ｂ１３抗原频率较对照组显著增高。结果表明：中国东北汉族胆石症患者与ＨＬＡ相关抗原为ＨＬＡ－Ｂ１３。进一步按结石部位、结石成分分组比较时，发现在各患者组中除了共同与ＨＬＡ－Ｂ１３抗原关联外，还分别与不同的ＨＬＡ抗原关联；胆囊结石与ＤＲ３；胆管结石与Ａ３、Ｂ３５；胆固醇结石与ＤＲ３；胆色素结石与Ａ３、ＤＲ７。结果提示胆囊结石，     

HLA and susceptibility to cervical neoplasia.

The association between cervical neoplasia and certain HLA phenotypes observed in different studies has not been consistent. By serological typing, the association between HLA antigens, cervical carcinoma and cervical intraepithelial neoplasia (CIN) was studied in a group of 172 and 116 patients, respectively. We demonstrated an increased frequency of B63 in patients with HPV types other than HPV 16 or 18, and B55 in patients that were negative for all HPV types. The association between cervical carcinoma and DQ3, described in various populations, was not observed in the present study. However, we confirmed other previously observed associations between cervical cancer and class II antigens, i.e., a positive correlation with DR15 irrespective of the HPV status, with DR3 in patients harboring HPV types other than HPV 16 or 18, and with DR11 among HPV 16 positive patients. In contrast, a negative correlation between DR13 and HPV positive cervical cancer was observed which suggests protection of this antigen against HPV-associated cervical cancer. A slight increase of DR15 and DQ4 antigens was observed in CIN patients, suggesting that these specific HLA antigens may be important in determining the risk of CIN.     

Association Between Major Histocompatibility Antigen and Reproductive Performance

ABSTRACT: Many studies have both supported and refuted an association between HLA antigens and reproductive performance. To clarify these discrepant results, HLA antigens from 59 couples experiencing recurrent spontaneous abortions and 79 couples with unexplained infertility were compared with 51 fertile couples. Patients with recurrent spontaneous abortions were classified as either primary (no children) or secondary (abortions after having children or stillbirths) aborters, and patients with unexplained infertility were classified as primary (never pregnant) or secondary (previously pregnant) infertiles. The amount of antigenic disparity, homozygosity, and the probability of producing a heterozygotic offspring were analyzed for each group. Significantly more disparities at combined HLA loci and at DR loci were observed when childbearing controls were compared with primary aborters. Significant disparity between controls and secondary aborters was at the DQ locus. Total homozygosity as well as homozygosity at DR and DQ loci were significantly increased among primary aborters, but not secondary aborters, and at the B locus among secondary, but not primary infertile couples. Significant association in probability of heterozygote production was seen at the DQ locus in patients with primary infertility. These results indicate that controversy involving association of HLA and reproductive performance can be explained by properly classifying recurrent spontaneous aborters and unexplained infertiles.     

HLA class I and II antigens in South African blacks with Graves' disease

A study was done to evaluate the relationship between Graves' disease and the HLA system in South African Blacks of Zulu descent. One hundred and three patients with Graves' disease and 1416 control subjects were typed for HLA A, B, and C antigens while HLA DR antigens were done on 63 of the former and 330 of the latter. There was a significant increase in the frequency of HLA DR3 in patients compared to control subjects (57.1% vs 36.1%; P corrected = 0.014). A relationship was also seen at the DR1 locus (14.3% vs 4.6%; P corrected = 0.023).     

Antiacetylcholine receptor and antinuclear antibodies in myasthenia gravis. Correlation with HLA, sex and Gm

Sera from 27 subjects with myasthenia gravis (MG) were examined by immunoassay for antibodies to double-stranded DNA (ds-DNA), RNA-nucleoprotein complexes (ENA) and acetylcholine receptor (ACHR). The prevalence of the genetic markers of sex, HLA and Gm were analyzed in relation to various parameters of these autoantibodies. The highest levels of ds-DNA antibodies were associated with HLA B8 as compared to other HLA antigens (p less than 0.05), females as compared with males (p less than 0.05), and females with HLA B8 (p less than 0.05) when both sex and HLA were analyzed concurrently. An association between low titers and HLA B7 (p less than 0.05), with a significant difference between the B8 females and B7 males (p less than 0.05) was also noted. By contrast, no Gm association was noted for antinuclear antibody parameters, but was observed in females between high ACHR antibody titers and the homozygous phenotype (3; 5, 13) (p less than 0.05). This study of MG implicated HLA and sex factors in the production of a broad spectrum of antinuclear antibodies, while the contrasting Gm association noted with ACHR antibody titers was indicative of distinctive immunogenetic influences over autoantibody production in MG.     

HLA-A, B, DR antigens and insulin-dependent diabetes in Algerians

HLA-A, B and DR antigens have been investigated in insulin-dependent diabetics and compared to controls in a population of Algerians. A decrease of A1 and DR2 and an increase of Aw 19.2; B8, B18 and especially DR3 were found in diabetics in comparison to controls. The strongest association was found for DR3, which is a good genetic marker of IDD (RR = 8.50) in this population. The frequency of some HLA antigen associations in IDD suggests that the diabetic gene(s) is linked to 2 main haplotypes: Aw 19.2; B18; DR3 and Aw 19.2; B8; DR3. Antigen DR4 was equally represented in IDD (21%) and controls (28.4%), but heterozygote DR3-DR4 was more frequent in diabetics. The relation between IDD and HLA antigens found in the Algerian population is very similar to that described in diabetic Caucasian populations of southern Europe, except for the lack of association with DR4.     

HLA antigens and susceptibility to myasthenia gravis

HLA-A, -B, -C and -DR antigen frequencies determined in a group of 73 myasthenia gravis (MG) patients were compared with those of a control group of 205 subjects. The strongest positive association with MG was found antigens B8 and DR3 (relative risks 9.56 and 8.84 respectively). Analysis of our data indicates that both antigens, independently from their linkage disequilibrium, are involved in susceptibility to MG. No relationship between HLA antigens on thymic pathology was observed in our material. In male MG patients the association with DR3 was weaker than in female patients. The difference in DR3 frequency between male and female patients was statistically significant; no significant difference was found for antigen B8. It appears that DR3 contributes to development of MG only in females. In male patients aged more than 30 years at the onset of disease, MG was not associated with B8 or DR3. In contrast, in female patients aged more than 30 years at the onset of disease there was a strong association of B8 and DR3 with the disease.     

HLA typing in classical and African Kaposi's disease

HLA A, B, C, typing have been done in 39 patients with clinically and histologically documented classical Kaposi's sarcoma. Thirty three were also typed for HLA DR antigens. Twenty seven were males, 12 were females and three ethnic groups were represented: european caucasoids 41%, north african caucasoids 38.5% and negroids 20.5%. The only statistically significant abnormality is an increase of HLA DR5 frequency (60.6 vs 26. p less than 0.001 et RR = 4.2). Such an increase has been evidenced also in AIDS patients, with or without Kaposi's sarcoma and then is not discriminant between all this different types of the disease.     

Association of HLA B27 antigen in Indian patients of ankylosing spondylitis and other autoimmune diseases

One thousand three hundred and forty clinically suspected patients of Ankylosing Spondylitis (AS) and other autoimmune diseases and 5000 controls were studied to detect the association of HLA B27 antigen amongst them. Other alleles studied include HLA B7, B40 (B60), B22(B55), B13, etc. Our findings show a considerable and consistent association of HLA B27 with AS irrespective of the community to which the patient, belonged his hygiene or socio-economic conditions. We also found that people in the age group of 21-39 were the most vulnerable, when number of affected individuals or severity of the disease were taken into consideration. Male members showed a preponderance over females in HLA B27 positivity. Detection of HLA B27 could help in the diagnosis of AS. Patients suffering from other autoimmune diseases such as rheumatoid arthritis, psoriasis, Reiter's syndrome and uveitis and patients with inflammatory bowel disease, colitis, eczema, bacillary or fungal infection were also found to be HLA B27 positive. A study of other alleles shows that even they sometimes associate AS and other autoimmune diseases.     

HLA—DR antigens and the rubella-specific immune response in man

Several genetic markers, HLA—A, B and DR antigens, Gm and Km types, and ABO blood types, were studied on 78 rubella seronegative schoolgirls immunized with "TO336" rubella vaccine. A marked association was found between an HLA haplotype, HLA—Aw24—Bw52—DRHO, and the low antibody responsiveness to rubella virus. The association with the DR antigen was thought to be primary to those with the HLA A or B antigens, suggesting that the gene(s) controlling the low responsiveness to rubella might be located near the HLA—DR locus in the human 6th chromosome. There was no statistically significant association between Gm, Km or ABO blood types and the rubella specific immune responsiveness as far as the primary in vivo antibody response was concerned.     

HLA antigens in IGA deficient paediatric patients

HLA antigens (A, B, C and DR loci) were studied in 62 IgA-deficient (IgAd) paediatric patients: 17 with coeliac disease (CD), 13 with juvenile arthritis (JA), 27 with frequent respiratory tract infections (RTI) and five with other diseases. The frequencies of HLA antigens in IgAd patients were compared with those in healthy blood donors, and in CD and JA patients with normal serum IgA levels. The IgA deficiency in the patients showed significant associations with HLA A1, B8, B13, Cw6, DR3 and DR7 (P less than 0.0005, P corr less than 0.02 vs controls) and decreased frequencies of DR2 (P less than 0.0005, P corr less than 0.02 vs controls). The HLA associations typical of coeliac disease, increased frequencies of HLA-B8 and DR3, were evident among the IgAd coeliacs; in contrast to the coeliacs with normal IgA levels, the IgAd coeliacs showed a significant increase of the HLA-Cw6 allele (P less than 0.0005, P corr less than 0.02 vs control coeliacs). Increased frequencies of HLA-A1, B8, B13, Cw6, DR3 and DR7 were noted in the patients with RTI, which can be explained by the frequent occurrence of the haplotypes A1, B8, DR3 and B13, DR7, the latter haplotype often also having the Cw6 allele. Among the IgAd JA patients, the antigen frequencies were similar to those in the JA patients with normal serum immunoglobulins.     

Histocompatibility Determinants in Israeli Jewish Patients with Coeliac Disease: Population and Family Study

The association between HLA and coeliac disease (CD) was studied in the Jewish population of Israel. A total of 112 patients were typed for HLA-A,B,C antigens, including 67 patients whose families were typed in order to deduce the genotypes. Forty-seven patients were typed for HLA-DR antigens. The HLA-A,B,C data show a pattern of association, which is similar to that found in European CD patients: HLA-B8 is increased, although to a lower degree; a suggestive, insignificant increase for Aw30, B13 and Cw6 and a decrease of Bw35 were noted. The DR antigens DR3 and DR7 are associated with CD in the Jewish population. An excess of DR3/DR7 heterozygotes was noted. The data from family and population studies support a model in which two different HLA-DR associated genes are intereacting.     

High frequency of altered HLA class I phenotypes in invasive breast carcinomas

We studied 105 tumor samples obtained from patients diagnosed as having breast carcinomas for HLA class I and II (DR) antigen expression, using a panel of mAbs defining HLA-monomorphic, locus-specific and allele-specific determinants. Peripheral blood lymphocytes from patients were also typed for HLA alleles. The results indicated total HLA class I losses in 55 patients (52.3%), HLA-A locus losses in four patients (3.8%), HLA-B locus losses in eight patients (7.6%), and A, B, locus losses in 10 patients (9.5%). The remaining 28 patients whose tissues reacted positively with monomorphic- and locus-specific mAbs were tested for HLA allelic losses using several anti-HLA mAbs defining A2, A3, A9, B8, B12, etc. Of these 28 patients, 16 (57%) showed one or more losses of HLA reactivity. These results indicated that in 88.5% of patients we detected a particular HLA-altered tumor phenotype. The downregulation of HLA class I antigens in breast carcinomas may thus be more frequent than previously reported, and patients without HLA class I downregulation may be the exception rather than the rule. It cannot be ruled out that HLA alterations are present in some of the 12 patients with an apparently normal HLA phenotype, as some HLA alleles could not be studied because of the lack of appropriate mAbs. These HLA alterations could represent an important step associated with tumor invasion, conferring to the tumor cells the ability to escape from T-lymphocyte recognition.     

Retinal vasculitis associated with HLA DR4. Brief definitive report

Inflammation of retinal blood vessels may be associated with a variety of systemic immune diseases. Despite the fact that a number of immunological abnormalities have been reported in patients with retinal vasculitis (RV), previous studies have failed to demonstrate an immunogenetic predisposition to this disease. HLA A, B, and DR locus typing of 25 patients (14 females) with well-characterized RV revealed an increased incidence of HLA DR4 (corrected p value = 0.04, relative risk = 3.5). The HLA DR4 antigen was increased in patients with both central and peripheral RV as well as in patients with idiopathic disease (14 patients) and in those with Behcet's syndrome (8 patients). The results of this study indicate that immune response genes may be involved in the pathogenesis of RV.     

HLA Phenotypes and joint affection in psoriasis, acute anterior uveitis and chronic prostatitis

In a prospective study, 50 patients hospitalized for psoriasis, 34 patients hospitalized for acute anterior uveitis (AAU) and 29 patients hospitalized for chronic prostatitis, were examined. The expected increased frequencies of HLA B13 and HLA B17 in psoriasis and of HLA B27 in AAU over healthy people were found. No unsuspected association between HLA antigens was observed. Psoriatic patients with peripheral joint affection frequently had affected sacro-iliac joints and were HLA B27 negative. Joint affection was frequently seen in HLA B27 positive patients with psoriasis or AAU. In the patients with AAU, 12 out of 22 patients positive for HLA B27 exhibited radiographical sacro-iliitis. This high prevalence of sacroiliitis suggests an interaction between genes predisposing for AAU and sacroiliitis. Asymptomatic sacro-iliitis was found in both HLA B27 positive and negative patients. The low frequency of clinical symptoms in psoriatic sacro-iliitis could not be explained by the absence of HLA B27.     

HLA antigens, psoriasis and acute anterior uveitis in Bechterew's syndrome (ankylosing spondylitis)

One hundred and twenty-two consecutively hospitalized patients with ankylosing spondylitis (AS) were reexamined. Ninety-two per cent were HLA B27 positive. Of the HLA B27 negative patients, 60% were found to have psoriasis, as opposed to 11 % of the HLA B27 positive patients. Acute anterior uveitis (AAU) was found only in HLA B27 positive patients, and more frequently in males than in females. The genetic and clinical heterogeneity of AS, together with the overlapping clinical criteria for AS and psoriatic spondylitis, may make the term "Bechterew's syndrome" preferable. Based on these findings and previous reports, we conclude that (i) AAU is a manifestation of Bechterew's syndrome in HLA B27 positive patients, (ii) HLA B27 negative patients without any obvious accompanying manifestations may suffer from psoriatic spondylitis, and (iii) genetic predisposition to psoriasis in persons who are HLA B13, B17 and B37 negative, may interact with the genetic predisposition to Bechterew's syndrome in HLA B27 positive persons and produce Bechterew's syndrome with psoriasis or psoriasis-like skin eruptions.     

Genetic markers in Australian Caucasian subjects with coeliac disease

A group of 69 unrelated Australian coeliac subjects (41 adult onset and 28 childhood onset) were typed for for HLA-A, B, DR and DQ antigens. Immunoglobulin allotypes were also determined in 36 of these patients. An association between coeliac disease and the antigens DR3, DR7 and DQw2 was confirmed in this population. There was no significant difference in antigen frequencies between childhood and adult onset coeliac disease, although the association with DR7 was stronger in the childhood group. All coeliac patients who did not carry DR3 or DR7 were found to be DR4 positive. No association was demonstrated between coeliac disease and any immunoglobulin allotype, either in the absence of HLA antigens B8 and DR3 or in male coeliac patients.