HLA-DQ A1, -DQB1 and -DRB1 gene polymorphism--in Malay type 1 diabetes mellitus patients and their use for risk prediction.

HLA-DQA1, -DQB1, and -DRB1 gene polymorphism were analyzed to study type 1 DM susceptibility in Malay patients from Southeast Asia (Malaysia and Singapore). Patients showed significant increases in the occurrence of DQA1*0501 (50.7% vs. 20.4%; RR = 3.97; Pc < 0.01), DQB1*0201 (48% vs. 19.1%; RR = 3.86; Pc < 0.05), and DRB1*0301 (38.7 vs. 6.8%; RR = 8.36; 95% Pc < 0.05). Conversely, significant decreases were noted in the occurrence of DQA1*0601 (14.7% vs. 35.2%; RR = 0.33; Pc = 0.008) and DQB1*0601 (4% vs. 23.5%; RR = 0.16; Pc < 0.05) in type 1 DM patients. Using a logistic regression model, we derived a risk prediction model for type 1 DM in our indigenous Malay population based on the identified HLA genotypes. The RR for type 1 DM increases by a factor of 5.68 for every unit increase in the number of DRB1*0301 allele (P < 0.001), and decreases by a factor of 0.18 per unit increase in the number of DQB1*0601 allele (P < 0.001). After adjusting for these two HLA genotypes, DQA1*0501, DQB1*0201 and DQA1*0601 were not statistically significant as risk predictors. The lower incidence of type 1 DM in the Malay population may be contributed by the genotypic combinations of DR and DQ genes as well as the linkage disequilibria between susceptible and protective alleles.

Novel brain reactive autoantibodies: prevalence in systemic lupus erythematosus and association with psychoses and seizures.

Autoantibodies can cause neuropsychiatric manifestations in lupus patients by altering the physiological function of neuronal cells. In this study, we identified Brain Reactive Autoantibodies (BRAAs) against murine neuronal membrane proteins (M.W. 27.5 and 29.5 kD) and found them correlating with psychosis and/or seizures in lupus patients. They were specific to neuronal membrane tissues of mammalian origin and are significantly associated with psychosis and/or seizures (p<0.0001). These membrane proteins mass spectrometry profiles did not match to any published protein sequences. These BRAAs may play important roles in the pathophysiology of neuropsychiatric lupus.

PCR-RFLP genotyping for exon 1 and promoter region mutations of the human mannose binding lectin (MBL-2) gene.

The Mannose Binding Lectin (MBL) plays an important role in innate immunity and its genetic deficiencies are associated with frequent and prolonged infections. Serum MBL determination may not accurately detect acute phase protein levels and it is also difficult to detect dysfunctional protein. Genotyping of the exon 1 and promoter regions in the MBL gene will provide useful information on the presence of deficiencies in patients. A reproducible PCR-RFLP method is described to accurately detect genotypes of exon 1 and polymorphic haplotypes of the promoter region in the MBL gene.

The sensitivity and specificity of autoantibodies to the Sm antigen in the diagnosis of systemic lupus erythematosus.

The anti-Sm test is thought to be specific for the diagnosis of systemic lupus erythematosus (SLE) and is one of the American College for Rheumatology (ACR) criteria for the classification of SLE. Locally, the sensitivity and specificity of this test for the diagnosis of SLE are unknown. We therefore aim to study the sensitivity and specificity of this test in our local context. A total of 1034 patient samples that were sent for routine testing of anti-Sm antibodies over a 30-month period, were included in the study. However, only 1031 patient samples were included in the final analysis as 3 casenotes were not traceable. Clinical diagnoses were obtained through a lupus database and chart review. Quantification of the anti-Sm antibodies was by the enzyme-linked immunosorbent assay (ELISA) technique. Positive anti-Sm test results were present in 165 samples, comprising 156 (94.5%) samples from lupus patients and 9 (5.5%) having diagnoses other than SLE. These diagnoses ranged from arthritis, overlap syndrome, Raynaud's phenomenon and cardiac-related diseases. The calculated sensitivity and specificity of the anti-Sm test, using a positive cut-off value of 20 units/ml, were 39.7% and 98.6%, respectively. If the positive cut-off value is raised to 30 units/ml, the specificity rises marginally to 99.5% but the sensitivity will drop by more than 10 percentage points to 27.2%. The anti-Sm test is not useful as a screening test for lupus but a positive result is highly specific for SLE.

Polymorphism of the regulatory region of tumour necrosis factor alpha gene in patients with systemic lupus erythematosus.

A single-base change in the regulatory region of the tumour necrosis factor alpha (TNF-alpha) gene and the TNF2 allele said to be associated with Caucasian lupus patients has been reported. We studied this genetic polymorphism in 89 normal individuals and 67 Chinese lupus patients, 45% of whom has renal involvement. The allelic frequencies of TNF1 and TNF2 alleles in our male controls (n = 49) were 0.86 and 0.14 respectively, in the female controls (n = 40) they were 0.91 and 0.09 respectively, and as a combined group they were 0.88 and 0.12 respectively. The corresponding frequencies in our lupus patients were 0.81 and 0.19 respectively. Comparing the allelic frequencies of the combined control and patient group as well as only between the female control and female lupus patients, we did not find any association between the TNF2 allele and systemic lupus erythematosus in our cohort of Chinese patients. The TNF2 gene may be in linkage disequilibrium with the DR3 allele.