HLA DRBI *DQB1* haplotype in HTLV-I-associated familial infective dermatitis may predict development of HTLV-I-associated myelopathy/tropical spastic paraparesis

A possible causal association between infective dematitis and HTLV-I infection was reported familial infective dematitis (ID) occurring in a 26-year-old mother and her 9-year-old son. The mother was first diagnosed with ID in 1969 at the age of 2 years in the Dermatology Unit at the University Hospital of the West indies (U.H.W.I.) in Jamaica. The elder of her 2 sons was diagnosed with ID at the age of 3 years, also at U.H.W.I. Both mother and son are HTLV-I-seropositive. A second, younger son, currently age 2 years, is also HTLV-I-seropositive, but without clinical evidence of ID. Major hitocompatibility complex (MHC), class II, human leucocyte antigen (HLA) genotyping documented a shared class II haplotype, DRB*DQBI* (1101-0301), in the mother and her 2 sons. This same haplotype has been described among Japanese patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), and has been associated with a possible pathologically heightened immune repsonse to HTLV-I infection. The presence of this haplotype in these familial ID cases with clinical signs of HAM/TSP may have contributed to their risk for development of HAM/TSP. The unaffected, HTLV-I seropositive younger son requires close clinical follow-up. (AU)

An investigation of HLA-encoded genetic susceptibility to multiple sclerosis in subjects of Asian Indian and Afro-Caribbean ethnic origin

The association of multiple sclerosis (MS) with the HLA class 11 loci DR and DQ was investigated in populations of Asian Indian and Afro-Caribbean ethnic origin, resident in the United Kingdom. The putative haplotype, DRB1*1501.DQA1*0102.DQBI*0602, was weakly positively associated with MS in both races. The overall contribution to disease susceptibility of this marker was small. Over 80 percent of MS patients in both racial groups did not possess this haplotype. The data suggest that other genetic and/or environmental factors may be more important in predisposing to MS in these two races. Our study also raises the possibility that genetically distinct forms of the disease may be expressed in white Caucasian and non-Caucasian populations (AU)

HLA association in Jamaica patients with myasthenia gravis - abstract

Thirty-two (32) Jamaicans with ocular or generalised myasthenia gravis (MG) as well as 40 normal controls were investigated for HLA-A, -B, -C and -DR antigens. HLA antigens contribution to relative risk (RR) in MG patients included HLA -A2 (RR = 615), HLA -B8 (RR = 3.4), HLA-13 (RR=7.76), HLA -DRw8 (RR = 1.34), HLAw12(RR = 1.89), HLA-DQw2(RR = 2.0), HLA -DQw3 (RR = 2.1) and HLA -DRw4 (RR = 3.8). The strongest associations were, therefore, HLA, -A2, -B8, -B13, DQw4. After correction of the 'P value" for the number of antigens tested, only HLA-A2, was significantly increased in MG patients compared to normal Jamaicans. The -DR3 haplo-type which is usually associated with auto-immune diseases was absent in Jamaican MG patients and present in only 5 percent controls. There was a paucity of auto-immune conditions associated with MG in this study. Several of the HLA associations found in Jamaican MG patients correspond to those found in other ethnic groups. However, HLA antigens associated with MG in Jamaican patients were more in agreement with those found in Japanese patients. The HLA types found in Jamaican MG patients did not correlate with thymic pathology, serum concentrations of acetylcholine receptor antibodies, clinical grades or disease course (AU)

HLA-DQA1 and DQB1 Alleles associated with genetic susceptibility to IDDM in a black population

Transracial analysis provides a method of distinguishing primary associations between insulin-dependent diabetes mellitus (IDDM) and HLA class II alleles from those secondary to linkage disequilibrium. Blacks show DR-DQ relationships that are different from other races and are a useful group in which to investigate HLA-D region associations with IDDM. In this study, the frequencies of HLA-DQA1 and -DQB1 alleles in Afro-Caribbean IDDM and control subjects were compared. Alleles were identified with sequence-specific oligonucleotide probing. The DQA1 allele A3 was positively associated with IDDM (relative risk[RR] = 25.3, corrected P [Pc]<7.0 x 10 -6). THe DQB1 alleles DQw2 and DQw8 were also positively associated (RR = 4.7, Pc<6.5 x 10 -3 and RR = 12.3,Pc = 3.4 x 10 -3, respectively). The A1.2 and DQw6 alleles were negatively associated (RR = 0.16, Pc<3.5 x 10 -3 and RR = 0.15, Pc = 2.4 x 10 -2, respectively). These findings were compared to data from other races. The positive associations with A3 and DQw2 are consistent with all racial groups investigated. The negative association with DQw6 is present in all racial groups in which it is a common allele. These findings suggest that DQ alleles, and hence DQ molecules, may directly affect predisposition to IDDM. (AU)

Trans-racial studies implicate HLA-DQ as a component of genetic susceptibility to Type 1 (insulin-dependent) diabetes

Type 1 (insulin-dependent) diabetic patients and control subjects of Afro-Caribbean Negroid racial origin were investigated by serological HLA-DR-typing and restriction fragment length polymorphism analysis using DNA probes corresponding to the DQO, DQá and DRá chain genes. Combined analysis indicated that four DR antigens are positively associated with the condition in Negroid subjects - DR3, 4, 7 and w9. DR3 and 4 are also associated in Caucasians, but the relative risk for DR3 is lower in Negroid subjects. The DR7 association is specific for the Negroid race, and DRw9 is only weakly associated in Caucasoid subjects. Restriction fragment length polymorphism analysis demonstrated a DQá restriction pattern in Negroid subjects which is absent from Caucasoid subjects. This pattern was associated with DRw9 and a subset of DR7, and was markedly increased in frequency in diabetic patients compared with control subjects (48.7 percent vs 10.4 percent respectively; p<10 -4). In the absence of this pattern, DR7 showed no positive association. DR3 in Negroid subjects was associated with two distinct DQO-DQá patterns, only one of which was positively associated with diabetes. A DQá pattern, in linkage disequilibrium with different DR antigens in different races, conferred a consistent protective effect against the development of Type 1 diabetes. Trans-racial genetic analysis thus supports a primary role for DQ in susceptibility to Type 1 diabetes. (AU)