Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Corixa (formerly Anergen), in collaboration with Organon, is developing AnergiX.RA, a complex of solubilized HLA DRB1-0401(a) together with a specific peptide from the human cartilage glycoprotein HCgp39, for the potential treatment of rheumatoid arthritis (RA) [307156]. Phase I/II trials were completed in April 2000 and the final results from the randomized, blinded, placebo-controlled dose-escalation study are expected later this year [363409]. The product utilizes Anergen's AnergiX technology, and combines an MHC-derived protein with an Organon autoantigen peptide, derived from myelin basic protein and involved in the development of RA [212659,363409]. Engagement of T-cell receptors with AnergiX.RA induces apoptosis in autoreactive T-cells [227421]. Researchers at Organon identified the central component in AnergiX.RA; results from preclinical studies identifying this target protein were published in June 1997 in Arthritis & Rheumatism. Researchers demonstrated that HC (human cartilage) gp39 is recognized by T-cells from RA patients and has the potential to block arthritis in the mouse model [248543,354821].
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PMID:AnergiX.RA Corixa. 1124 98

The influence of HLA DRB1 alleles on B-cell homeostasis was analyzed in 164 patients with rheumatoid arthritis (RA). The percentages of CD19+ B lymphocytes determined in the peripheral circulation of 94 retrospectively recruited RA patients followed a bimodal distribution. Two frequency peaks (B-cell(low) patients and B-cell(high) patients) were separated by the population median of a B-cell frequency of 8.5% of all lymphocytes. Human leucocyte antigen genotyping revealed that the B-cell(low) patients were more frequently positive for the RA-associated HLA DRB1 shared epitope (SE) than were B-cell(high) patients. Accordingly, SE-positive patients had lower CD19 percentages in the rank-sum analysis when compared with SE-negative patients, and were markedly B lymphocytopenic when compared with a healthy control group. To confirm the differential frequencies of CD19+ B cells, absolute numbers in peripheral blood were determined prospectively in a cohort of 70 RA patients with recent onset disease. SE-positive patients were found to have lower absolute numbers of circulating CD19+ B cells. B-cell counts below the mean of the study population were associated with higher acute phase response and with increased levels of rheumatoid factor IgA. No correlation between absolute numbers of circulating B cells and radiographic progression of joint destruction was seen. The influence of immunogenetic parameters on B-cell homeostasis in RA reported here has not been described previously. The clinical relevance of B lymphocytopenia in SE-positive RA will be further investigated in longitudinal studies.
Arthritis Res 2002
PMID:B lymphocytopenia in rheumatoid arthritis is associated with the DRB1 shared epitope and increased acute phase response. 1210

The prevalence of rheumatoid arthritis (RA) is relatively constant in many populations, at 0.5-1.0%. However, a high prevalence of RA has been reported in the Pima Indians (5.3%) and in the Chippewa Indians (6.8%). In contrast, low occurrences have been reported in populations from China and Japan. These data support a genetic role in disease risk. Studies have so far shown that the familial recurrence risk in RA is small compared with other autoimmune diseases. The main genetic risk factor of RA is the HLA DRB1 alleles, and this has consistently been shown in many populations throughout the world. The strongest susceptibility factor so far has been the HLA DRB1*0404 allele. Tumour necrosis factor alleles have also been linked with RA. However, it is estimated that these genes can explain only 50% of the genetic effect. A number of other non-MHC genes have thus been investigated and linked with RA (e.g. corticotrophin releasing hormone, oestrogen synthase, IFN-gamma and other cytokines). Environmental factors have also been studied in relation to RA. Female sex hormones may play a protective role in RA; for example, the use of the oral contraceptive pill and pregnancy are both associated with a decreased risk. However, the postpartum period has been highlighted as a risk period for the development of RA. Furthermore, breastfeeding after a first pregnancy poses the greatest risk. Exposure to infection may act as a trigger for RA, and a number of agents have been implicated (e.g. Epstein-Barr virus, parvovirus and some bacteria such as Proteus and Mycoplasma). However, the epidemiological data so far are inconclusive. There has recently been renewed interest in the link between cigarette smoking and RA, and the data presented so far are consistent with and suggestive of an increased risk.
Arthritis Res 2002
PMID:Epidemiology and genetics of rheumatoid arthritis. 1211 Jan 46

The HLA system is being paid more and more attention because it is very significant in polymorphous immunological reactions. Several studies have suggested that genetic susceptibility to rheumatic fever (RF) and rheumatic heart disease (RHD) is linked to HLA class II alleles. We hypothesized that HLA class II associations within RHD may be more consistent if analysed amongst patients with a relatively homogeneous clinical outcome. A total of 70 RF patients under the age of 18 years were surveyed and analysed in Latvia. HLA genotyping of DQA1, DQB1 and DRB1 was performed using PCR with amplification with sequence-specific primers. We also used results from a previous study of DQB1 and DRB1 genotyping. In the RF patients, HLA class II DQA1*0401 was found more frequently compared to DQA1*0102. In the RF homogeneous patient groups, DQA1*0402 has the highest odds ratio. This is also the case in the multivalvular lesion (MVL) group, together with DQA1*0501 and DQA1*0301. In the chorea minor patients, DQA1*0201 was often found. Significant HLA DQA1 protective genotypes were not detected, although DQA1 genotypes *0103/*0201 and *0301/*0501 were found significantly and frequently. In the distribution of HLA DRB1/DQA1 genotypes, *07/*0201 and *01/*0501 were frequently detected; these also occurred significantly often in the MVL group. The genotype *07/*0201 was frequently found in Sydenhamn's chorea patients that had also acquired RHD, but DRB1*04/DQA1*0401 was often apparent in RF patients without RHD. In the distribution of HLA DQA1/DQB1 genotypes, both in RF patients and in the homogeneous patient groups, the least frequent were *0102/*0602-8. The genotype DQA1*0501 with the DQB1 risk allele *0301 was often found in the MVL group. The genotype *0301/*0401-2 was frequently found in the RF and Sydenhamn's chorea patient groups. The haplotype *07-*0201-*0302 was frequently found in RF and homogeneous patient groups, including the MVL group. In addition, haplotypes *04-*0401-*0301 and *04-*0301-*0401-2 were frequent amongst patients with Sydenhamn's chorea. The protective alleles DQA1*0102 and DQB1*0602-8 in the haplotype DRB1*15 were less frequently found in RF patients. The results of the present study support our hypothesis and indicate that certain HLA class II haplotypes are associated with risk for or protection against RHD and that these associations are more evident in patients in clinically homogeneous groups.
Arthritis Res Ther 2007
PMID:HLA class II DR and DQ genotypes and haplotypes associated with rheumatic fever among a clinically homogeneous patient population of Latvian children. 1755 88

The genetic components contribute to the systemic lupus erythematosus development. This study for the first time determined the distribution of the polymorphisms and linkage disequilibrium in HLA class II, MICA and PRL gene among patients suffering from SLE and healthy Czech individuals. DNA was obtained from the peripheral blood cells of 123 SLE patients and 96 healthy people. Allele variants of the HLA class II, MICA transmembrane polymorphism and PRL extrapituitary promoter -1149G/T SNP were detected using the sequence-specific primers analysis, PCR-fragment analysis and PCR-RFLP, respectively. In Czech population, only DRB1*03-DQB1*0201 haplotype is significantly associated with increased risk for SLE development: the frequency in SLE group was 44.7% in comparison with 15.2% in controls, P (c) < 0.0001; OR 4.54 CI 95% (2.36-9.09). The MICA-A5.1 allele is present significantly more often in SLE (55.7%) than controls (39.9%), P (c) = 0.005; OR 1.88 CI 95% (1.29-2.77), and the combination of HLA DRB1 *03 together with MICA-A5.1 is strongly associated with SLE [P (c) < 0.000001; OR 9.71 CI 95% (3.4-27.7)]. On the other hand, the MICA-A6 allele is less frequent in SLE patients compared to controls, 10.6% and 19.7%, respectively [P (c) = 0.035; OR 0.48 CI 95% (0.28-0.82)], and the combination of absence both alleles MICA-A6 and HLA DRB*11 seems to be risk for SLE development compared to controls, 84.6 and 70.2%, respectively, [P (c) = 0.0003 OR 2.32 CI 95% (1.47-3.70)]. We found that only G allele of the -1149 G/T SNP is associated with specific clinical manifestation of SLE, arthritis [P (c) = 0.022; OR 2.63, CI 95% (1.45-4.81)]. HLA class II-MICA combinations may increase/decrease a risk for SLE development. Multiple studies focusing on the ethnical differences as well as genetic-epigenetic relationships are necessary for better understanding SLE pathogenesis.
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PMID:HLA class II, MICA and PRL gene polymorphisms: the common contribution to the systemic lupus erythematosus development in Czech population. 2035 25