Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036421 (PSS)
 10,989 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previous studies in Caucasians with progressive systemic sclerosis (PSS) have suggested associations of antitopoisomerase I (antitopo I) autoantibodies with either serologically defined HLA-DR2 or DR5. To better define class II HLA associations with the antitopo I response, 161 PSS patients (132 Caucasians and 29 American blacks) were studied for antitopo I autoantibodies by immunodiffusion and immunoblotting, and their HLA-DRB1, DRB3, DQA1, and DQB1 alleles were determined by restriction fragment length polymorphic analysis and DNA oligotyping. Among Caucasians with antitopo I, HLA-DR5(DRB1*1101-*1104), DRB3*0202 and DQw3 (DQw7,8,9) were significantly increased in frequency. In American blacks, however, only HLA-DQB1*0301(DQw7) was significantly increased. The presence of HLA-DQB1*0301(DQw7) and other HLA-DQB1 alleles bearing the uncharged polar amino acid residue tyrosine at position 30 of the outermost domain was found in all antitopo I-positive Caucasian PSS patients compared with 66% of antitopo I-negative PSS patients (pc = 0.007) and 70% of normal controls (pc = 0.008), as well as all antitopo I-positive black patients. The association with HLA-DQB1 was independent of HLA-DR5(DRB1*1101-*1104) or any other HLA-DRB1, DRB3, or DQA1 alleles. Alternative or additional candidate epitopes for this autoimmune response include alanine at position 38 and threonine at position 77 of these same DQB1 alleles. These data suggest that genetic predisposition to the antitopo I response in PSS is associated most closely with the HLA-DQB1 locus.
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PMID:Association of amino acid sequences in the HLA-DQB1 first domain with antitopoisomerase I autoantibody response in scleroderma (progressive systemic sclerosis). 132 3

HLA antigen distribution was studied in 126 patients with systemic sclerosis (SSc) followed prospectively and compared to that of 325 healthy controls. The frequencies of HLA antigens DR3, DR5 and DRw52 were increased in patients with diffuse skin involvement (P = 0.02, 0.05, 0.03). The presence of DRw52 (relative risk [RR] much much greater than 1) and DRw6 (RR = 54.5) was associated with significantly increased risks of a fatal disease outcome with pulmonary hypertension (PHT). In the absence of PHT, DRw252 was inversely associated with the risk of death. These findings indicate an adverse prognosis in SSc when PHT is present in association with DRw52.
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PMID:HLA alleles in systemic sclerosis: association with pulmonary hypertension and outcome. 152 26

HLA class II alleles (detected by DNA typing) were determined in 116 Caucasians with systemic sclerosis positive and negative for anticentromere autoantibodies (ACA). Significantly increased frequencies of HLA-DR5(DRw11) (P = 0.009) and the Dw13(DRB1*0403, *0407) subtypes of DR4 (probability corrected, Pc = 0.005) were seen in ACA positive patients, and HLA-DR1 and DRw8 were also increased. These findings appeared to reflect linkage disequilibrium of DR5(DRw11) and many DR4(Dw13) haplotypes with HLA-DQw7 and DR1 with DQw5. In fact, the presence of a DQB1 allele having a polar glycine or tyrosine at position 26 of the DQB1 first domain versus a hydrophobic leucine accounted for 100% of ACA positive Caucasian systemic sclerosis patients compared to 69% of the ACA negative SS patients (P = 0.0008) and 71% of Caucasian controls (P = 0.0003) as well as all 7 ACA patients of non-Caucasian background. Furthermore, the genotype frequency of DQB1 alleles lacking leucine at position 26 was 73% in ACA positive SS patients, compared to 42% of ACA negative patients (P = 1.2 x 10(-5)) and 38% of controls (P = 5.8 x 10(-7)). These data, then, suggest that the second hypervariable region of the HLA-DQB1 chain may form the candidate epitope associated with the ACA response.
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PMID:Association of polar amino acids at position 26 of the HLA-DQB1 first domain with the anticentromere autoantibody response in systemic sclerosis (scleroderma). 155 82

The distribution of Gm allogenotypes (Gm allotypes identified by IgCH restriction fragment length polymorphism (RFLP) analysis) was compared in 66 systemic lupus erythematosus (SLE) patients, 38 CREST/PSS group (P less than 0.05) but not in the SLE group. HLA-DR5 is significantly increased in frequency in this series of CREST/PSS patients compared to controls (P less than 0.001), and log linear regression analysis showed that although both DR5 and Gm homozygosity were significant factors determining disease susceptibility, there was no evidence of an interactive effect between these two groups of genes increasing the predisposition to CREST/PSS.
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PMID:Gm allogenotype distribution and lack of HLA-DR, Gm interaction in SLE and CREST/PSS. 257 39

The HLA-DR locus of the major histocompatibility complex encodes class II molecules which participate in immune responses through regulation of T cell interaction with antigen presenting cells. Previous association studies between HLA-DR antigens and the autoimmune disease, systemic sclerosis (or scleroderma), have yielded conflicting results. Some investigators have reported an association between this disease and HLA-DR1, while others have demonstrated an association with HLA-DR5. In this study, we used restriction fragment length polymorphisms in the HLA-DR locus to compare allelic frequencies of HLA-DR1 and HLA-DR5 in scleroderma patients with diffuse disease and healthy control subjects. No significant difference in the allelic frequency of either antigen was observed between the groups. These results suggest that HLA-DR1 and HLA-DR5 antigens are unlikely to contribute significantly to disease susceptibility in scleroderma.
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PMID:Lack of an association between diffuse systemic sclerosis and HLA-DR1 or HLA-DR5. 257 46

We report a small kindred in which the father and daughter with positive antinuclear antibodies (ANA) (proband) had diffuse cutaneous and visceral scleroderma (systemic sclerosis, SSc), antitopoisomerase autoantibodies and shared the HLA-A23 C- B- DR5 DRw52 DQw3 haplotype. The ANA- granddaughter (daughter of the proband) was noted to have severe isolated pulmonary hypertension within the first 6 months of life, and had the other maternal HLA-A1 Cw8 B14 DR1 DQw1 haplotype, which included a B1, B2 duplication of the C4B allele. All 3 members shared DRw52. The possibility that neonatal pulmonary hypertension represents an isolated autoimmune disease or a hitherto undescribed neonatal syndrome is proposed and the immunogenetic autoantibody implications are discussed.
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PMID:Isolated pulmonary hypertension in the grandchild of a kindred with scleroderma (systemic sclerosis): "neonatal scleroderma"? 262 83

Of 397 systemic sclerosis (scleroderma) patients from the University of Pittsburgh, who had serum determinations of both anti-Scl-70 and anticentromere antibody (ACA), 26% had anti-Scl-70 and 22% had ACA. No patient had both autoantibodies. Weak associations with HLA-DR5 and HLA-DR1 were detected with anti-Scl-70 and ACA, respectively. ACA was found almost exclusively (96%) in patients with limited cutaneous scleroderma (the CREST syndrome variant), but the majority (57%) of patients with limited scleroderma did not have this antibody. Among patients with limited scleroderma, those with ACA more often had calcinosis and telangiectasias and less often had pulmonary interstitial fibrosis and restrictive lung disease. However, the frequency of pulmonary hypertension and the survival rates were similar in the ACA+ and ACA- limited scleroderma patients. Two-thirds of patients with anti-Scl-70 had diffuse scleroderma, but only 33% of all diffuse scleroderma patients had this antibody. Within the subset of diffuse scleroderma, anti-Scl-70 was associated with peripheral vascular disease (digital pitting scars) and pulmonary interstitial fibrosis, but was not predictive of cardiac or renal involvement or survival. ACA and anti-Scl-70 are useful in diagnosing and classifying systemic sclerosis variants and in predicting the natural course of the disease. Their mutually exclusive occurrence suggests either 2 separate clinical entities or important host factors determining their production.
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PMID:Clinical correlations and prognosis based on serum autoantibodies in patients with systemic sclerosis. 334 23

Immunogenetic markers, autoantibodies, and clinical features were studied in 47 patients, 35 Caucasian and 12 black, with systemic sclerosis. Twenty-two had generalized scleroderma, while 25 had limited skin involvement. HLA-DR1 (RR = 2.1, p = 0.08) and DR5 (RR = 2.1, p = 0.08) were increased in Caucasian patients vs controls as was the supertypic specificity HLA-DRw52 (RR = 2.8, p = 0.02, pc = 0.04). HLA-DR6.1 was increased in black patients vs controls (RR = 15.4, p = 0.008, pc = 0.088). There were no significant increases in any of the complement allotypes in either racial group. Anticentromere antibody was noted in 10 patients, all Caucasian; 7 had limited disease. Anti-Scl-70 was noted in 4 patients; all had generalized disease (p = 0.036). HLA-DR2 was present in all anti-Scl-70 positive patients (RR = 22.5, p = 0.006). Our results suggest that clinical subsets of systemic sclerosis can be defined by genetic and serological markers.
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PMID:Systemic sclerosis (scleroderma): clinical, genetic, and serologic subsets. 347 51

Allotyping of the major histocompatibility complex (MHC)-linked complement component C4 has revealed a strong association of the null allele, C4A*Q0, with systemic sclerosis (SSc). Sixty-four percent of patients with SSc carried the C4A*Q0 allele, compared with 17% of the control group. Twenty-five patients and their families were typed for HLA antigens (A, B, Cw, and DR) and the MHC-linked complement components C4 and factor B to identify haplotypes in the MHC linkage group and C4 null alleles. Strong allelic association of HLA-B8 and DR3 with C4A*Q0 probably explains the previously reported association of SSc with the extended haplotype carrying HLA-B8 and DR3. Ninety-two percent of the patients had either C4A*Q0 or DR5; 31% of the controls had either C4A*Q0 or DR5.
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PMID:A strong association between null alleles at the C4A locus in the major histocompatibility complex and systemic sclerosis. 349 Feb 65

The HLA-A, B, C, and DR loci of 136 patients with progressive systemic scleroderma have been determined. The patients were classified according to the extent of their skin affection and into groups with or without immunologic and inflammatory signs of the disease. The antigens of the A locus did not show any significant deviations in frequency of occurrence. An increase of HLA-B8 and HLA-DR3 was only proved in the male patient group. Furthermore, in the HLA-DR gene locus, an increase in frequency of HLA-DR1, 2, 3, and 5 could be found. However, in the total set of patients, only the correlation of HLA-DR5 with progressive systemic scleroderma reached significance. Patients suffering from the CREST (calcinosis, Raynaud's phenomenon, esophagus, sclerodactyly, and telangiectasia) syndrome showed an increase of HLA-DR1. Patients with inflammatory signs of the scleroderma showed an accumulation of HLA-DR2. Several HLA-linked genes control the susceptibility to scleroderma.
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PMID:Association of progressive systemic scleroderma to several HLA-B and HLA-DR alleles. 349 40


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