Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies to fibrin-bound tissue plasminogen activator (tPA) have been found in autoimmune diseases with vascular injury, such as systemic lupus erythematosus and scleroderma. The purpose of this study was to determine whether patients with primary pulmonary hypertension (PPH) have an immunogenetically determined response to fibrin-bound tPA. Antibodies to fibrin-bound tPA were determined in three patient groups: 45 adults with PPH, 41 children with PPH, and 40 children with anatomically large congenital pulmonary to systemic communications (PHT+shunt). The frequencies of the HLA class II (DRB1,3,4,5, and -DQB1) alleles in these three patient groups were compared with those of 51 healthy Caucasian control subjects. Fibrin-bound tPA antibodies were found in four of 45 (9%) adults with PPH, four of 41 (10%) children with PPH, and one of 40 (2.5%) children with PHT-shunt. HLA class II typing, which was available for seven of nine Caucasians with fibrin-bound tPA antibodies, revealed that six of seven (86%) patients typed HLA-DQ7 (DQB1*0301) and one typed HLA-DQ6. The 86% frequency of HLA-DQ7 in the antibody positive patients was significant compared with the 29% frequency in the healthy control subjects (p = 0.007, p corrected [pc] = 0.05, OR = 14.4). Of interest, these antibody-positive patients, although lacking antiphospholipid antibodies, shared an amino acid epitope, common to HLA-DQB1*06,07 and 08 subtypes, which was previously reported to be associated with the lupus anticoagulant. In conclusion, antibodies to fibrin-bound tPA and HLA-DQ7, and possibly the same epitope associated with the lupus anticoagulant, defined a small subset of children and adults with PPH.
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PMID:Primary pulmonary hypertension, tissue plasminogen activator antibodies, and HLA-DQ7. 900 24

Neonatal lupus erythematosus (NLE) is a rare disorder of neonates characterized by two major clinical manifestations: congenital heart block and cutaneous lupus lesions. The disease is associated with placentally transferred maternal anti-Ro/SSA and/or La/SSB antibodies. To clarify possible class II HLA associations with maternal autoantibody responses, haplotypic and allelic distributions, along with the polymorphism of the MHC class II HLA alleles, were analyzed based on PCR-RFLP results in 25 Japanese mothers of two groups defined by precipitating autoantibody profiles. Among mothers with both anti-Ro/SSA and anti-La/SSB antibodies, but not those with anti-Ro/SSA alone, the class II haplotypes DRB1*1101-DQA1*0501-DQB1*0301 and DRB1*08032-DQA1*0103-DQB1*0601 as well as individual class II alleles DRB1*1101, DRB1*08032 and DQB1*0301 showed significantly increased frequencies compared to those in normal controls. All anti-Ro/SSA and anti-La/SSB positive mothers carried DRB1 alleles that shared the same amino acid residues at positions 14-31 and 71 of the DRB1 chain. These mothers also carried homozygous or heterozygous DQ6 and DQ3 alleles that shared the same amino acid residues at positions 27-36 and 71-77 of hypervariable regions of the DQB1 chain. Furthermore, all mothers with both anti-Ro/SSA and anti-La/SSB were homozygous for DPB1*0501. Nine of 10 anti-Ro/SSA and anti-La/SSB-positive mothers, but only 6 of 15 mothers with anti-Ro/SSA alone, had affected infants. Thus, our findings suggest that there may be immunogenetic differences among mothers according to their autoantibody profiles, and that mothers with both anti-Ro/SSA and anti-La/SSB are more likely to have infants with NLE than mothers with anti-Ro/SSA alone.
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PMID:Neonatal lupus erythematosus: studies on HLA class II genes and autoantibody profiles in Japanese mothers. 954 18

To investigate the role of HLA-DQ2 in the pathogenesis of associated immune disorders, we generated transgenic mice that expressed HLA-DQ2 in the absence of endogenous murine class II molecules (AE(0)DQ2). These AE(0)DQ2 mice with a mixed genetic background spontaneously developed skin lesions on their ears, whereas control AE(0)DQ6 genotype control mice (also with a mixed genetic background) did not. The skin lesions were characterized by deep subepidermal blistering with hydropic degeneration and lymphoid infiltration in the subepidermal area as determined by histopathology. Immunofluorescence analysis revealed thick band-like granular deposition of IgG, IgM, and a thin band of IgA deposition along the basement membrane. AE(0)DQ2 mice also developed significant and progressive hematuria and proteinuria as compared with the AE(0)DQ6 mice (p < 0.05). Histopathology showed immune complex deposits in the glomeruli of AE(0)DQ2 mice. Immunofluorescence analysis showed progressive mesangial and capillary wall deposition of IgA, IgM, IgG and C1q in the kidney. With electron microscopy, the deposits showed a 'fingerprint' substructure; and tubuloreticular structures were identified within endothelial cells. Conversely, these changes were not observed in AE(0)DQ6 mice. Serum anti-double stranded (ds)DNA IgM and IgG levels were also significantly elevated among AE(0)DQ2 mice compared with AE(0)DQ6 mice (p < 0.001). In conclusion, AE(0)DQ2 mice spontaneously develop an autoimmune lupus-like syndrome and are useful model for this disease. It remains to be determined whether genetic admixture played a role in the development of this systemic lupus erythematosus-like syndrome in HLA-DQ2 transgenic mice. Lupus (2010) 19, 815-829.
Lupus 2010 Jun
PMID:Spontaneous lupus-like syndrome in HLA-DQ2 transgenic mice with a mixed genetic background. 2014 96