Purified proteins from Leishmania amastigotes-induced delayed type hypersensitivity reactions and remission of collagen-induced arthritis in animal models.

A treatment preparation composed of purified Leishmania (L) antigenic fractions (AS210) induced linear delayed type hypersensitivity (DTH) reactions over a 1-40 microg dose range, in guinea pigs. When a DBA-1 mouse collagen induced arthritis (CIA) model was used to compare AS210 treatment against: a polyvalent vaccine (AS110-1), a monovalent vaccine (AS110-2) and placebo, the AS210 treated mice had the least amount of forepaw inflammation and the lowest mean arthritis scores (MAS). When MAS for day(s) 1-40 were analyzed using one way ANOVA, statistically significant (P < 0.05) differences were seen for the following study groups: PBS versus Dexamethasone and PBS versus AS210. Subsequently, the ANOVA analysis results were corroborated by the Mann-Whitney test: analysis of the first group (P < 0.001) and analysis of the second group (P < 0.001). Comparison between dexamethasone and AS210 at different time intervals by Mann-Whitney test were as follows: day 0-day 5 both treatments had equal values (P = 1.00), from day-7 to 20 AS210 treatment had lower MAS values than dexamethasone (P = 0.037), and from day-21 to 30, AS210 MAS were similar to dexamethasone values (P = 0.319). No statistical difference was observed between AS110-1, AS110-2, and placebo groups.

Antigens from Leishmania amastigotes induced clinical remission of psoriasis.

While injecting volunteers in Venezuela with a vaccine for prevention of leishmaniasis, we observed 100% clinical remission of a psoriatic lesion in one subject. Subsequently, the vaccine (AS100) was evaluated in psoriatic patients with an open label, single center study. The study was conducted in 2,770 subjects and included plaque (79%), guttate (10%), plaque and guttate (10%), palm/plantar, erythrodermia, inverse, plaque and arthritis and nail psoriasis. Baseline PASI compared with post-treatment values were: PASI 100, 23%; PASI 75, 45%; PASI 50, 13%; PASI 10, 9% and

HLA-C(*)03 is a risk factor for cardiomyopathy in Chagas disease.

Previous studies have shown the effect of class 1 as detected by serology or class 2 HLA genes by oligotyping upon susceptibility or resistance to the cardiomyopathy that develops in approximately one third of the Trypanosoma cruzi chronically infected patients. Low and intermediate resolution DNA typing of class 1 alleles was performed in a sample of 113 serologically positive individuals with and without cardiomyopathy. A polymerase chain reaction-sequence-specific oligonucleotide probe method using primers and probes from the British Society of Histocompatibility and Immunogenetics as modified for the VII Latin American Histocompatibility Workshop by D. Middleton, and LiPA kits from Innogenetics were used. Several alleles (A(*)11, A(*)31, B(*)15, B(*)35, B(*)45, B(*)49, B(*)51, and C(*)03) showed increased frequencies among patients with cardiac damage versus the asymptomatic group, but only the last one remained significant after correction of the p value (OR = 5.8, p(c) = 0.03). HLA-C(*)03 showed linkage disequilibrium with B(*)40 and B(*)15 and although both haplotypes were increased in cardiopathic patients compared with asymptomatic individuals, the difference is not significant. These results suggest that the HLA-C*03 allele could confer susceptibility to the development of cardiomyopathy among Venezuelan T. cruzi seropositive individuals and contrast with the protective effect conferred by the HLA B40 Cw3 haplotype among Chilean chagasic patients. Further studies will be needed to confirm the role of this allele on the cardiomyopathy of Chagas disease.

HLA class II DRB1, DQB1, DPB1 polymorphism and cardiomyopathy due to Trypanosoma cruzi chronic infection.

Trypanosomiasis is an important cause of cardiomyopathy in endemic rural areas of Latin America. Previous studies have suggested participation of HLA molecules in the immune response regulation of T. cruzi infection, and association of HLA antigens with heart damage. One hundred and eleven unrelated T. cruzi antigen-seropositive individuals were tested for HLA class II alleles by the polymerase chain reaction and sequence specific oligonucleotide (PCR-SSO) method. Patients were classified in 3 groups according to clinical and electrocardiographic characteristics: asymptomatics (group A), with arrhythmia (group B), and with overt congestive heart failure (group C). Statistical analysis confirmed the significant increment of the DRB1*01 DQB1*0501 haplotype (p = 0.03) previously reported by our laboratory in patients with cardiomyopathy. The DPB1*0401 allele frequency is also significantly increased in patients with heart disease (groups B + C) (p = 0.009) while DPB1*0101 frequency is higher among the asymptomatic group (p = 0.04) compared with individuals of group C. The DPB1*0401 allele in homozygous form or in combination with allele DPB1*2301 or 3901, was found present more often in patients of groups B and C. Thus, the combination of two of these three alleles, sharing specific sequence motifs in positions 8, 9, 76, and 84-87 confers a relative risk of 6.55 to develop cardiomyopathy in seropositive patients (p = 0.041). Furthermore, 32% of the cardiomyopathics have either DRB1*01 DQB1*0501 and/or DPB1*0401/*0401, 0401/*2301, or* 0401/*3901 compared with 9% of the seropositive asymptomatics (OR = 5.0; p = 0.006).