The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia.

Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-γ, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL-10 were higher, the levels of TGF-ß were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia.

IL1RN VNTR and IL2-330 polymorphic genes are independently associated with chronic immune thrombocytopenia.

Chronic Immune Thrombocytopenia (cITP) is an acquired immune-mediated disease associated with a T-helper cell type 1 (Th1) immune polarization, whose genetic risk factors, however, are largely unknown. We investigated polymorphisms in promoter regions of genes that code molecules involved in proinflammatory immune response [IL1B-31T/C, IL1RN variable number tandem repeats (VNTR), IL2-330T/G, and TNF-307G/A] as well as in genes that code Toll like receptors (TLR) (TLR2 Arg753Gln, TLR4 Asp299Gly and TLR5 Arg(392stop)) in 122 patients with cITP and 541 blood donors. The frequencies of the IL1RN polymorphic allele 2 (P = 0·001) and of the IL2-330 polymorphic allele G (P =0·004) were significantly higher in cITP patients than in blood donors. In logistic analysis adjusting for age and gender, the polymorphisms remained independently associated with cITP. Enhanced serum concentrations of interleukin (IL)-1α and IL-1ß were observed in cITP (P < 10(-3) ) and blood donor (P = 0·04) carriers of the IL1RN*2. Also, the serum levels of IL-2 and γ-interferon (IFN-γ) were increased in cITP patients (P < 10(-3) and P = 0·04 respectively) and blood donors (P < 10(-3) and P = 0·03 respectively) harbouring the IL2-330G allele. Here we demonstrated that IL2-330G and IL1RN*2 are independently associated with cITP and are functional in vivo, which strongly suggests that they contribute to the pathogenesis of cITP.

The serum levels of the cytokines involved in the Th17 and Th1 cell commitment are increased in individuals with borderline thrombocytopenia.

The definition of immune Thrombocytopenia (ITP) as a peripheral blood platelet count less than 100 × 109/L instead of the historical criteria of 150 × 109/L renders subjects with platelets between 100 and 150 × 109/L without a diagnosis. Here, we demonstrated that these subjects have enhanced levels of proinflammatory cytokines linked to Th1 and Th17 cell response, and are more frequently carriers of polymorphisms in genes that code cytokines involved in the commitment of Th1 and Th17 immune response, when compared with controls, similarly to that observed in patients with ITP.

Long-term effect of Helicobacter pylori eradication on plasma homocysteine in elderly patients with cobalamin deficiency.

BACKGROUND: Helicobacter pylori gastritis may lead to impairment of the production of pepsinogen and acid, which are essential to cobalamin absorption. In turn, cobalamin deficiency leads to hyperhomocysteinaemia, a risk factor for cardio and cerebrovascular diseases. AIM: To evaluate the effect of H pylori eradication on plasma homocysteine levels in elderly patients. PATIENTS: Sixty-two H pylori-positive elderly patients with cobalamin deficiency were prospectively studied. METHODS: Homocysteine and cobalamin concentrations were determined before, 6 and 12 months after H pylori eradication. RESULTS: Corpus atrophy was observed in a few patients; otherwise, in most of them, the degree of corpus gastritis was moderate to severe. The initial homocysteine mean (SD) levels decreased from 41.0 (27.1) to 21.6 (10.1) micromol/l at the 6 month follow-up (p<0.001) and to 13.1 (3.8) micromol/l 12 months after H pylori eradication (p<0.001). Conversely, initial cobalamin mean levels increased from 145.5 (48.7) pmol/l to 209.8 (87.1) pmol/l and to 271.2 (140.8) pmol/l, 6 and 12 months after treatment, respectively (p<0.001 for both). Although the erythrocyte mean corpuscular volume was within reference intervals, it decreased significantly 6 (p = 0.002) and 12 (p<0.001) months after treatment. CONCLUSIONS: The results of the current study demonstrated that the eradication of H pylori in elderly patients with cobalamin deficiency is followed by increasing of cobalamin and decreasing of homocysteine blood levels.

Estudo prognóstico em pacientes portadores de leucemia linfocítica crônica (LLC) / Prognostic factor in chronic lymphocytic leukemia (CLL)

Introdução e objetivo: a LLC, neoplasia clonal de células B, é a leucemia mais freqüente nos países ocidentais. Este trabalho avalia retrospectivamente as características clínicas dos portadores de LLC no Serviço de Hematologia do Hospital das Clínicas da UFMG. Metodologia: foram analisados os prontuários médicos de 77 pacientes com diagnóstico de LLC de 1992 a 2005. Resultados: dentre dos pacientes estudados 47 eram do sexo masculino (61%) e 30 (39%) do sexo feminino. A sobrevida média foi de 115 meses, a idade mediana de 65 anos, variando de 38 a 91 anos. A anormalidade citogenética mais freqüente foi a trissomia do 12, presente em 16% dos pacientes que apresentaram metáfases para análise. O sistema de estadiamento de Raí modificado foi o que melhor se correlacionou à sobrevida (p=0,001) e mostrou baixo risco – 21 pacientes (27,2%); risco intermediário – 36 pacientes (46,7%) e alto risco – 20 pacientes (25,9%), com sobrevida média de 154 meses, 65 meses e 43 meses, respectivamente. Entre as variáveis, nenhuma se mostrou significante em análise multivariada. Dez pacientes (13%) não haviam recebido quimioterapia até o momento do estudo e 67 (87%) foram tratados com esquemas de mono ou poliquimioterapia. Os pacientes tratados receberam clorambucil, fludarabina, fludarabina associada à ciclofostamida, COP, CHOP e radioterapia. Conclusão: não houve diferença significante na sobrevida entre as diversas formas de tratamento.