Visceral leishmaniasis (VL) caused by Leishmania chagasi is endemic to northeast Brazil. A positive delayed-type hypersensitivity skin test response (DTH þ ) is a marker for acquired resistance to disease, clusters in families and may be genetically controlled. Twenty-three single nucleotide polymorphisms (SNPs) were genotyped in the cytokine 5q23.3-q31.1 region IRF1-IL5-IL13-IL4-IL9-LECT2-TGFBI in 102 families (323 DTH þ ; 190 DTHÀ; 123 VL individuals) from a VL endemic region in northeast Brazil. Data from 20 SNPs were analyzed for association with DTH þ /À status and VL using family-based, stepwise conditional logistic regression analysis. Independent associations were observed between the DTH þ phenotype and markers in separate linkage disequilibrium blocks in LECT2 (OR 2.25; P ¼ 0.005; 95% CI ¼ 1.28-3.97) and TGFBI (OR 1.94; P ¼ 0.003; 95% CI ¼ 1.24-3.03). VL child/parent trios gave no evidence of association, but the DTHÀ phenotype was associated with SNP rs2070874 at IL4 (OR 3.14; P ¼ 0.006; 95% CI ¼ 1.38-7.14), and SNP rs30740 between LECT2 and TGFBI (OR 3.00; P ¼ 0.042; 95% CI ¼ 1.04-8.65). These results indicate several genes in the immune response gene cluster at 5q23.3-q31.1 influence outcomes of L. chagasi infection in this region of Brazil.

HLA-DRB1, -DRB3, -DQA1 and -DQB1 alleles were determined by DNA typing in 51 Scandinavian patients with systemic lupus erythematosus (SLE) and 129 controls. DRB1*03,DRB3*0101,DQA1*0501,DQB1*0201 were significantly increased in the patient group, with relative risks (RR) of 2.80, 3.07, 3.55 and 2.12, respectively. These alleles are in strong linkage disequilibrium, and their possible relative contributions in predisposition to SLE are difficult to distinguish. The strongest association was found for DQA1*0501, which is in linkage disequilibrium with DRB1*03 as well as DRB1*11,12 (DR5). An increased frequency of DRB1*11,12 was observed (RR = 1.89, ns). No association with DRB1*15,16 (DR2) was found. The patients had a higher frequency of HLA class II homozygosity than the controls (RR = 5.05, p = 0.0005). When compared to the low-risk group (nonDRB1*03 class II heterozygotes), the cases homozygous for DRB1*03,DQA1*0501,DQB1*0201, known to be in linkage disequilibrium with the complement allele C4A*Q0, had the highest relative risk of developing SLE (RR = 16.39, p = 0.0002). However non[DRB1*03,DQA1*0501,DQB1*0201] class II homozygotes had a higher relative risk (RR = 4.68, p = 0.0147) than DRB1*03,DQA1*0501,DQB1*0201 heterozygotes, known to carry the C4A*Q0 allele (RR = 2.72, p = 0.0088). This may suggest that HLA class II molecules are directly involved in susceptibility to SLE.

The idiopathic generalized epilepsies (IGE) occur with a high aggregation within families. Juvenile myoclonic epilepsy (JME) is recognized as a commonly occurring form of idiopathic generalized epilepsy. A possible association between JME and HLA antigens was investigated by serological typing of human leukocyte antigens (HLA) class I antigens and by DNA oligotyping of class II antigens. Twenty-four patients and 129 controls, all Caucasians of Scandinavian descent, were tested. Uncorrected there was a significant positive association (Relative risk (RR) = 8.07) to B17 and a significant negative association (RR = 0.13) to B8 as well as DRB1*3. The negative association to DQ alleles DQA1*0501 and DQB1*0201, which are in strong linkage disequilibrium with the alleles B8 and DRB1*3, was weaker and not significant, thus giving no clue as to a primary HLA-DQ association of JME.