HLA-B27 is strongly associated with ankylosing spondylitis (AS) but the role of the HLA molecule itself is still unclear. In this study on Singapore Chinese, we have subtyped 50 B27 positive AS patients and 45 B27 positive normals and found that the B*2706 allele has a significant negative association with disease (p = 0.047). Together with recent data indicating the existence of AS "protective" B27 alleles, our data shows that the HLA molecule itself plays a crucial role in disease development.
We reviewed the case records of 10 Oriental patients with systemic lupus erythematosus (SLE) who developed pulmonary haemorrhage (PH) between 1987 and 1996 to determine their clinical presentation and outcome. All the patients had clinical evidence of PH including a sudden onset of dyspnoea, tachycardia, fall in haemoglobin (at least 1.5 gm%) and bilateral diffuse alveolar infiltrates on chest radiographs. At the time of PH, nine patients had a disease duration of 2 years or less and all the patients had clinical and/or laboratory evidence of active lupus disease. Fever and lung crepitations were present in 90% of patients while haemoptysis and chest pain occurred in only three and two patients, respectively. All the patients were treated with high dose intravenous corticosteroids and in addition seven had a combination of pulse methylprednisolone and cyclophosphamide, and four had received plasmapheresis. Four patients died as a result of PH. One patient died of pneumonia three years after recovering from PH while the remaining five had no recurrence of PH after a median follow-up of 22 months. Our study suggests that PH in Oriental lupus patients often occurs early in the disease, rarely presents with haemoptysis and has a high mortality despite aggressive immunosuppressive therapy.
The clinical and laboratory features of 61 oriental male lupus patients were compared to those of 86 oriental female patients to determine whether gender differences occur. Arthritis was significantly less common in the males. Neuropsychiatric disorders were less frequent but the difference did not reach statistical significance. Renal disease was the commonest clinical manifestation and diffuse proliferative glomerulonephritis the dominant histological finding on renal biopsy in the males. The prevalences of leucopenia and antibodies to extractable nuclear antigens in particular anti-Ro (SSA) and anti-La(SSB), were lower in men. Arthritis and serositis were less common in our oriental males in contrast to the caucasian patients. These findings provide further evidence of differences between the genders in SLE and suggest racial factors may affect clinical presentation.
This study analysed HLA class 1 and 2 allele associations in Singaporean Chinese patients with RA. Seventy patients (ARA definite or classical) and 80 controls were typed for HLA class 1 alleles by serology and class 2 alleles by serology and the PCR/SSO method. RA patients had higher frequencies of DRB1*0405 (40 vs 12.5%; corrected probability value (PC) < 0.02, relative risk (RR) = 4.7, 95% confidence limit (CL) 2.1-10.6), DRB1*1001 (14.3 vs 1.3%; PC = 0.06, RR = 13.2, 95% CL 1.6-105.7), DQB1*0401 (38.6 vs 12.5%; P = 0.006, RR = 4.4, 95% CL 1.9-10.0) and DQB1*0501 (20 vs 5%; PC = 0.048, RR = 4.8, 95% CL 1.5-15.2). It is concluded that Chinese RA is associated primarily with HLA DRB1*0405 and DRB1*1001 which share common amino acid sequences in the third hypervariable region of the DR beta chains shown to be associated with RA in other ethnic groups. Patients without DRB1*0405 and *1001 had a higher frequency of DRB1*0901, which is in linkage disequilibrium with HLA B46 in the Chinese.
The recommendations developed by a formal group consensus method may be useful for clinical practice and guiding funding decisions by relevant authorities in making bDMARD usage accessible and equitable to eligible patients in Singapore.
A validated and feasible consensus process can enable pragmatic standardized recommendations to be developed for bDMARD subsidization for AS patients in a local Asian context.
Objectives-To characterise the cytoplasmic staining patterns identified by indirect immunofluorescence (IF) of human epithelial (HEp-2) cells and the antigens recognised using additional serological techniques. To define the disease associations of anticytoplasmic antibodies. Methods-Sera from 1173 patients were screened for cytoplasmic IF staining on HEp-2 cells and the patterns characterised. The presence of antimitochondrial antibodies (AMA) was evaluated by a sensitive anti-pyruvate dehydrogenase complex enzyme linked immunosorbent assay (ELISA) (IgG) and by immunoblotting. Detection of antibodies to extractable nuclear antigens (ENA) was performed by double immunodiffusion and the presence of anti-ribosomal P antibodies was determined by immunoblotting. Results-Cytoplasmic IF staining was demonstrated in 75 sera (6-4%). Six different patterns were recognised: coarse granular filamentous speckles (AMA, n = 9); condensed large speckles (anti-golgi apparatus antibodies, n = 3); cytoskeletal (n = 9); centriolar (n = 4); diffuse coarse speckles (n = 33); and fine speckles (n= 17). Of the nine sera with an AMA pattern, the presence of these antibodies was confirmed in seven by the ELISA (n=6) and on immunoblotting (n= 7). One of the seven patients had primary biliary cirrhosis, and two had scleroderma. Two patients with anti-golgi antibodies had rheumatoid arthritis and two with anticentriolar antibodies had scleroderma. Of 33 sera that had cytoplasmic staining and were ANA negative, three were positive for anti-Ro and two were positive for anti-Jo-I antibodies. Conclusions-In general, defined cytoplasmic IF patterns have no specific disease associations. However, the finding of cytoplasmic fluorescence should not be ignored, as it may indicate the presence of antibodies to ENA in the absence of nuclear staining.
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