Toxoplasmic encephalitis: role of Human Leucocyte Antigens/alleles associated with rapid progression to Acquired Immunodeficiency Syndrome

Abstract Background/aims The frequency of Human Leucocyte Antigens/alleles associated with rapid progression from Human Immunodeficiency Virus infection to Acquired Immunodeficiency Syndrome was evaluated in Brazilian patients with Acquired Immunodeficiency Syndrome with and without Toxoplasmic Encephalitis. Methods 114 patients with Acquired Immunodeficiency Syndrome (41 with Toxoplasmic Encephalitis, 43 with anti-Toxoplasma gondii antibodies, without Toxoplasmic Eencephalitis, and 30 without anti-Toxoplasma gondii antibodies circulating and without Toxoplasmic Encephalitis) were studied. Results Human Leucocyte Antigens/alleles associated with rapid progression to Acquired Immunodeficiency Syndrome, particularly HLA-B35, -DR3, and -DR1 allele group, were significantly less represented in patients with Toxoplasmic Encephalitis and Acquired Immunodeficiency Syndrome. Conclusion The presence of these Human Leucocyte Antigens/Alleles that predispose to Acquired Immunodeficiency Syndrome progression was associated with resistance to Toxoplasmic Encephalitis among Human Immunodeficiency Virus-1 carriers.

Susceptibility to toxoplasmic retinochoroiditis is associated with HLA alleles reported to be implicated with rapid progression to AIDS.

BACKGROUND/AIMS: The frequency of HLA markers associated with rapid progression to AIDS was evaluated in Brazilian patients with AIDS exhibiting or not toxoplasmic retinochoroiditis (TRC). METHODS: 98 AIDS patients (25 with TRC, 43 with anti-T. gondii antibodies but without TCR, and 30 without anti-T. gondii antibodies and without TCR) were studied. RESULTS: The HLA-B35 was significantly increased in TRC group (p=0.0038). CONCLUSION: The presence of HLA-B35 may simultaneously predispose to progression to AIDS and TRC.

HLA class I haplotypes and progression of primary open-angle glaucoma.

PURPOSE: To verify if patients with primary open-angle glaucoma with HLA class I haplotypes (A9-B12, A2-B40, A1-B8) associated with this disease may have a greater rate of progression than patients who do not present these haplotypes. METHODS: Anatomical and functional glaucoma evaluation (cup-to-disc ratio and visual field) of 25 patients (six of them with one of the haplotypes associated with glaucoma) followed at the Glaucoma Outpatient Clinic of the University Hospital, Ribeirão Preto School of Medicine, São Paulo University (HCFMRP-USP) for ten years after typing of their HLA antigens in order to compare with their previous condition. RESULTS: A greater increase of the cup-to-disc ratio was observed in patients with HLA haplotypes associated with primary open-angle glaucoma predisposition. However, no significant differences in functional damage progression or in retinal nerve fibers loss were detected between them and other patients with glaucoma. CONCLUSION: The present results indicate an association of class I HLA haplotypes with progression of anatomic alterations of the optic nerve head in glaucomatous patients.

HLA class I haplotypes and progression of primary open-angle glaucoma / Haplotipos HLA de classe I e progressão do glaucoma primário de ângulo aberto

PURPOSE: To verify if patients with primary open-angle glaucoma with HLA class I haplotypes (A9-B12, A2-B40, A1-B8) associated with this disease may have a greater rate of progression than patients who do not present these haplotypes. METHODS: Anatomical and functional glaucoma evaluation (cup-to-disc ratio and visual field) of 25 patients (six of them with one of the haplotypes associated with glaucoma) followed at the Glaucoma Outpatient Clinic of the University Hospital, Ribeirão Preto School of Medicine, São Paulo University (HCFMRP-USP) for ten years after typing of their HLA antigens in order to compare with their previous condition. RESULTS: A greater increase of the cup-to-disc ratio was observed in patients with HLA haplotypes associated with primary open-angle glaucoma predisposition. However, no significant differences in functional damage progression or in retinal nerve fibers loss were detected between them and other patients with glaucoma. CONCLUSION: The present results indicate an association of class I HLA haplotypes with progression of anatomic alterations of the optic nerve head in glaucomatous patients.

OBJETIVO: Verificar se pacientes com glaucoma primário de ângulo aberto portadores de haplotipos HLA de classe I (HLA - A9-B12; -A2-B40; e -A1-B8) associados a essa doença poderiam ter progressão maior do que pacientes que não apresentassem esses haplotipos. Método: Avaliação anatômica e funcional de 25 pacientes (6 dos quais com um dos haplotipos associados a glaucoma), seguidos no Ambulatório de Glaucoma do Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCFMRP-USP), por dez anos depois da tipificação de seus antígenos HLA, para comparação com as condições anteriores. RESULTADOS: Houve aumento maior da relação escavação/disco em pacientes com haplotipos HLA associados com predisposição para glaucoma primário de ângulo aberto, no entanto não foram encontradas diferenças significantes entre esses e outros pacientes com glaucoma na progressão do dano fisiológico e nem na perda de fibras nervosas da retina. CONCLUSÃO: Os resultados indicam a associação de haplotipos HLA de classe I com maior taxa de progressão das alterações anatômicas da cabeça nervo óptico em pacientes com glaucoma.

Immunohistochemical expression of HLA-DR in the conjunctiva of patients under topical prostaglandin analogs treatment.

PURPOSE: Subclinical inflammation may be observed in patients using topical antiglaucomatous drugs. The objective of this study was to investigate inflammation in conjunctiva of glaucoma patients using prostaglandin analogs, by the detection of an immunogenetic marker (HLA-DR) and compare the effect of 3 different drugs: latanoprost, bimatoprost, and travoprost in the induction of this inflammation. SUBJECTS AND METHODS: Thirty-three patients with primary open-angle glaucoma were evaluated without and with prostaglandin analogs topical therapy. Imprints of conjunctival cells were obtained, fixed on glass slides, and prepared for immunohistochemical analysis. RESULTS: Before the use of prostaglandin analogs, 4 of the 33 patients evaluated presented expression of HLA-DR in the conjunctiva (mild). After 1 month on prostaglandin analog treatment, all but 1 patient presented HLA-DR staining. HLA-DR expression of these 32 patients was scored as mild (19 patients), medium (11 patients), or intense (2 patients). The differences were statistically significant both when the presence and the increased expression of HLA-DR were considered (P<0.001). When the 3 different groups were analyzed (latanoprost, bimatoprost, and travoprost) no statistically significant difference was found (P=0.27). CONCLUSIONS: The use of prostaglandin analogs eye drops provokes a subclinical inflammatory reaction, observed by HLA-DR expression, even after a short period of treatment, independently of the class of the prostaglandin analogs used.

HLA profile in patients with AIDS and tuberculosis.

Studies carried out in various populations have reported an association between some HLA specificities and susceptibility to tuberculosis. We investigated the class I and class II HLA profile in Brazilian patients of various ethnic backgrounds who had AIDS and tuberculosis. Twenty-two adult patients with AIDS and tuberculosis (Group I), 103 patients with AIDS without tuberculosis (Group II) and 423 healthy individuals not infected with HIV (Group III) were evaluated. Diagnosis of HIV infection was made by ELISA, confirmed by a gelatin particle agglutination test. Diagnosis of tuberculosis was made based on clinical/radiological presentation and direct bacilloscopy or clinical specimen cultures. Class I antigens were typed by microlymphotoxicity. Class II alleles were characterized by the polymerase chain reaction (PCR). Differences in frequency of HLA specificities between groups were found in the following antigens/alleles: Group I x Group II: HLA-A31 - p=0.026; HLA-B41 - p= 0.037; HLA-DRB1*10 - p=0.037; HLA-DQB1*5 - p=0.009. Group I x Group III (control): HLA-A31 - p = 0.000008; odds ratio (OR)=31.75; HLA-B41 - p=0.003; HLA-DQB1*5 - p=0.02. HLA-A31 and HLA-B41 antigens and the HLA-DRB1*10 and HLA-DQB1*05 alleles were over-represented in patients with AIDS and tuberculosis (Group I), suggesting that these HLA molecules are associated with susceptibility to tuberculosis in Brazilian patients with AIDS.

HLA profile in patients with AIDS and tuberculosis

Studies carried out in various populations have reported an association between some HLA specificities and susceptibility to tuberculosis. We investigated the class I and class II HLA profile in Brazilian patients of various ethnic backgrounds who had AIDS and tuberculosis. Twenty-two adult patients with AIDS and tuberculosis (Group I), 103 patients with AIDS without tuberculosis (Group II) and 423 healthy individuals not infected with HIV (Group III) were evaluated. Diagnosis of HIV infection was made by ELISA, confirmed by a gelatin particle agglutination test. Diagnosis of tuberculosis was made based on clinical/radiological presentation and direct bacilloscopy or clinical specimen cultures. Class I antigens were typed by microlymphotoxicity. Class II alleles were characterized by the polymerase chain reaction (PCR). Differences in frequency of HLA specificities between groups were found in the following antigens/alleles: Group I x Group II: HLA-A31 - p=0.026; HLA-B41 - p= 0.037; HLA-DRB1*10 - p=0.037; HLA-DQB1*5 - p=0.009. Group I x Group III (control): HLA-A31 - p = 0.000008; odds ratio (OR)=31.75; HLA-B41 - p=0.003; HLA-DQB1*5 - p=0.02. HLA-A31 and HLA-B41 antigens and the HLA-DRB1*10 and HLA-DQB1*05 alleles were over-represented in patients with AIDS and tuberculosis (Group I), suggesting that these HLA molecules are associated with susceptibility to tuberculosis in Brazilian patients with AIDS.