Combined effects of CXCL8 and CXCR2 gene polymorphisms on susceptibility to systemic sclerosis

A previous study suggested that the CXCR2 (+1208) TT genotype was associated with increased risk of systemic sclerosis (SSc). In the present study, we investigated the influence of variation in the CXCL8 and CXCR2 genes on susceptibility to SSc and combined the variant alleles of these genes to analyze their effects on SSc. Methods: One fifty one patients with SSc and 147 healthy bone marrow donors were enrolled in a casecontrol study. Blood was collected for DNA extraction; typing of CXCL8 (251) T/A and CXCR2 (+1208) T/ C genes was made by polymerase chain reaction with sequence specific primers (PCR-SSP), followed by agarose gel electrophoresis. Results: The CXCR2-TC genotype was significantly less frequent in patients (23.8% versus 55.1% in controls; P < 0.001, OR = 0.26, 95%CI = 0.15–0.43), whereas the CXCR2-CC genotype was significantly more frequent (44.4% versus 22.4% in controls; P < 0.001, OR = 2.76, 95%CI, 1.62–4.72). When CXCR2 and CXCL8 combinations were analyzed, the presence of CXCR2 T in the absence of CXCL8 A (CXCR2 T+/CXCL8 A) was more frequent in patients than in controls (34.5% versus 3.5%; P < 0.001, OR = 14.50, 95%CI = 5.04– 41.40). However, CXCR2 TT and CXCL8 A were significantly more common in controls (100%) than in patients (58.3%) (P < 0.001). Likewise, the presence of CXCR2 TC and CXCL8 A was more frequent in controls (95.1%) than in patients (75%) (P = 0.004). Furthermore, the CXCR2-CC genotype in CXCL8 A was more frequent in patients (59.7% versus 0% in controls; P < 0.001, adjusted OR = 98.67, 95%CI = 6.04– 1610.8). In patients, a high frequency was observed in combination with the CXCL8 TA and AA genotypes (P < 0.001; OR = 28.92), whereas in controls, there was a high frequency of combination with CXCL8 T (P < 0.001; OR = 0.03) and TT (P < 0.001; OR = 0.01). ). Conclusions: These findings suggest a protective role of CXCL8 (251) A in the CXCR2 (+1208) TT and TC genotypes and an increased risk of CXCL8 (251) A in association with the CXCR2 (+1208) CC genotype in SSc patient

Haemophagocytic lymphohistiocitosis : treatment with plasmapheresis and intravenous immunoglobulin

O presente relato de caso tem como finalidade chamar a atenção de doença grave que frequentemente é confundida com septicemia, no entanto o mecanismo etiológico é decorrente de defeitos genéticos ou associados à resposta imunológica exagerada, decorrente de ação citotóxica de linfócitos T CD8 e histiócitos, acarretando proliferação clonal e ativação de células ”natural killer” (NK). Uma tempestade de linfocinas acontece e como consequência é iniciada uma incontrolável hemofagocitose de todos os elementos sanguíneos, terminando pela infecção secundária do organismo por ausência de destruição de patógenos. A maioria dos casos termina pela morte do paciente; no entanto, relatamos nesse caso a possibilidade de incluirmos a plasmaferese como forma de retirar as linfocinas circulantes, razão do estímulo à destruição celular. O tratamento concomitante com alta dose de imunoglobulina endovenosa também foi realizado.The purpose of the present case report is to call attention to a serious disease that is often mistaken with septicemia, although its etiological mechanism results from genetic defects or is associated with an immune over-reaction, resulting from cytotoxic action of CD8 T lymphocytes and histiocytes, causing clonal proliferation and activation of “natural killer” (NK) cells. There occurs a storm of lymphokines and, as a consequence, an uncontrollable hemophagocytosis of all blood elements, which leads to secondary infection of the organism because of absence of pathogens destruction. Although most of the cases end up in death, in this case we report the possibility of including plasmapheresis as a way to remove the circulating lymphokines, the reason for stimulation of cell destruction. Co-treatment with high dose of intravenous immunoglobulin was performed too

Molecular analysis of pathogens in cerebrospinal fluid by the polymerase chain reaction in HIV-infected patients

Introdução: A reação em cadeia da polimerase (PCR) foi teste de grande impacto no diagnóstico das meningites e encefalites linfocíticas durante a última década. Esse método foi extensivamente usado no diagnóstico das infecções do sistema nervoso central (SNC), devido a sua habilidade em detectar amostras mínimas de DNA-alvo no líquido cefalorraquiano. Objetivo: O objetivo deste estudo foi identificar a prevalência dos patógenos oportunistas responsáveis por causar problemas neurológicos em pacientes infectados com o vírus da imunodeficiência humana (HIV) e avaliar sua associação com os achados clínicos, laboratoriais e da tomografia computadorizada cerebral (TCC). Pacientes e métodos: Um estudo transversal foi realizado em 203 amostras de líquido cefalorraquiano (LCR) de pacientes do sul do Brasil infectados com HIV e com aparente encefalite e meningite linfocíticas. As amostras foram analisadas para os seguintes agentes pelo método da reação em cadeia da polimerase “nested” ou dupla (N-PCR): citomegalovírus, vírus do Epstein-Barr, vírus do herpes simplex tipos 1 e 2, vírus da varicella zoster, vírus do herpes humano tipo 6, vírus JC, Toxoplasma gondii e micobactérias. Resultado: Pelo menos um patógeno foi encontrado em 77 (38%) dos indivíduos. O Epstein-Barr foi o mais prevalente, com 40 casos (19,7%), seguido pelo citomegalovívus, com 12 casos (15%) e pelo vírus JC, em 9 casos (4,4%). Um N-PCR positivo mostrou associação com aumento de proteínas e de celularidade (P=0,001), meningismo (P=0,017) e tomografia computadorizada anormal (P=0,006). Conclusão: O painel de PCR empregado foi efetivo na identificação de infecções neurológicas severas em pacientes HIV positivos.Introduction: Polymerase chain reaction (PCR) has had great impact on the diagnosis of lymphocytic meningitis and encephalitis over the last decade. It has been extensively used in the diagnosis of central nervous system (CNS) infections for its ability to detect small amounts of target DNA in the cerebrospinal fluid (CSF). Objective: The aim of this study was to identify the prevalence of opportunistic pathogens responsible for neurological disorders in patients infected with human immunodeficiency virus (HIV) and to evaluate its association with clinical, laboratory and cerebral computed tomography (CCT) findings. Patients and methods: A cross-sectional study was performed on 203 cerebrospinal fluids (CSF) from HIV-infected patients from Southern Brazil, with apparent lymphocytic meningitis and encephalitis. CSF samples were analyzed with probes for cytomegalovirus, Epstein-Barr virus, herpes simplex virus types 1 and 2, varicella zoster virus, human herpes virus type 6, JC virus, Toxoplasma gondii and mycobacterium in nested polymerase chain reaction (N-PCR). Results: At least one pathogen was found in 77 (38.0%) individuals. Epstein-Barr virus was the most prevalent with 40 cases (19.7%), followed by cytomegalovirus with 12 cases (5.9%) and JC virus with 9 cases (4.4%). Positive NPCR showed association with high spinal fluid protein and cell count (P=0.001), meningism (P=0.017) and abnormal CCT (P=0.006). Conclusion: The PCR panel used was effective in screening several neurological infections in HIV positive patients

Humoral immune response in adult Brazilian patients with mucolipidosis III gamma

Mucolipidosis II and III (ML II and III) alpha/beta and ML III gamma are lysosomal diseases caused by GlcNAc-1-phosphotransferase deficiency. Previous data indicate that MLII patients have functionally impaired immune system that contributes to predisposition to infections.We evaluated the immunological phenotype of three Brazilian patients with ML III gamma. Our data suggest that the residual activity of GlcNAc-1-phosphotransferase in patients with ML III gamma is enough to allow the targeting of the lysosomal enzymes required for B-cell functions maintenance