B-Cell Responses in Chronic Chagas Disease: Waning of Trypanosoma cruzi-Specific Antibody-Secreting Cells Following Successful Etiological Treatment.

BACKGROUND: A drawback in the treatment of chronic Chagas disease (American trypanosomiasis) is the long time required to achieve complete loss of serological reactivity, the standard for determining treatment efficacy. METHODS: Antibody-secreting cells and memory B cells specific for Trypanosoma cruzi and their degree of differentiation were evaluated in adult and pediatric study participants with chronic Chagas disease before and after etiological treatment. RESULTS: T. cruzi-specific antibody-secreting cells disappeared from the circulation in benznidazole or nifurtimox-treated participants with declining parasite-specific antibody levels after treatment, whereas B cells in most participants with unaltered antibody levels were low before treatment and did not change after treatment. The timing of the decay in parasite-specific antibody-secreting B cells was similar to that in parasite-specific antibodies, as measured by a Luminex-based assay, but preceded the decay in antibody levels detected by conventional serology. The phenotype of total B cells returned to a noninfection profile after successful treatment. CONCLUSIONS: T. cruzi-specific antibodies in the circulation of chronically T. cruzi-infected study participants likely derive from both antigen-driven plasmablasts, which disappear after successful treatment, and long-lived plasma cells, which persist and account for the low frequency and long course to complete seronegative conversion in successfully treated participants.

Initial functional status predicts infections during steroid therapy for renal diseases.

BACKGROUND AND AIM: Corticosteroid therapy is an effective way of treatment for many renal diseases, however, it is sometimes associated with infections. Our aim is to identify useful predictive markers of infection during steroid therapy. METHODS: We examined 121 patients (M/F = 71/50, mean age 43.8, range 15 - 82 years) who were treated with corticosteroids (IgA nephropathy in 51, minimal-change disease in 17, membranous nephropathy in 16 rapidly progressive glomerulonephritis (RPGN) in 13, lupus nephritis in 12 and other disorders in 12). Karnofsky's performance score (KPS) was employed to assess the physical functional status at the time of diagnosis. Infections were defined as conditions that required more than 1-week care, and those that caused the patient's death. RESULTS: Nineteen patients (15.7%) had infections during treatment. A logistic multivariate analysis showed significant correlations between infection and the use of immunosuppressive agents (relative risk RR = 7.7, p = 0.0265), ages of 52.9 years or more (RR = 13.5, p = 0.0026), initial number of lymphocytes (Lym) less than 1.250/microl (RR = 14.2, p = 0.0011), and KPS less than 77.4 (RR = 12.1, p = 0.0020). All correlations with infection were independent of all the other variables listed above. CONCLUSION: KPS, along with age, Lym and the use of immunosuppressive agents, are useful for the prediction of infectious complications during steroid therapy.

Close relationship of plasminogen activator inhibitor-1 4G/5G polymorphism and progression of IgA nephropathy.

BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1) 4G/4G genotype influences the development of diabetic nephropathy and lupus nephritis. However, the association of the PAI-1 4G/4G genotype and IgA nephropathy (IgAN) has not been investigated. SUBJECTS AND METHODS: The PAI-1 and ACE polymorphisms were examined in 270 healthy volunteers and 202 biopsy-proven IgAN patients, including 117 untreated IgAN patients who had an annual health check, allowing an estimation of the time of onset of overt proteinuria and/or hematuria. The relationship between the gene polymorphisms and the pathogenesis of IgAN were examined in 202 IgAN patients and the relationship between the gene polymorphisms clinical and pathohistological findings were examined in 117 untreated IgAN patients cross-sectionally at the time of renal biopsy. RESULTS: 202 IgAN patients and 117 untreated IgAN patients did not have different frequencies in PAI-1 4G/5G (4G/4G : 4G/5 : 5G/5G = 82 : 90: 30, 45 : 55 : 17) and ACE I/D (DD : ID : II = 41 : 82 : 79, 21 : 54 : 42) gene polymorphisms compared with 270 healthy volunteers (4G/4G : 4G/5 : 5G/5G = 99 : 124 : 47, DD : ID : II = 53 : 106 : 111). However, IgAN with 4G/4G had significantly more advanced histological changes than IgAN with 4G/5G or 5G/5G both in glomerular and tubulointerstitial findings (p < 0.0005). The disease duration in IgAN with 4G/4G was shorter than in IgAN with 4G/5G + 5G/5G (6.22 +/- 6.38 and 8.80 +/- 9.79 years, respectively, p < 0.05). Creatinine clearance (Ccr) in IgAN with 4G/4G was significantly lower than IgAN with 4G/5G or 5G/5G (72.3 +/- 26.5 and 82.4 +/- 22.8 ml/min, respectively, p < 0.05). The mean urinary protein excretion in IgAN with 4G/4G was significantly more than in IgAN with 4G/5G or 5G/5G (1.10 +/- 1.48 and 0.70 +/- 1.01 g/day, respectively, p < 0.05). There was no difference between IgAN with the DD ACE genotype and IgAN with ID + II genotypes in either the clinical or histopathological findings. CONCLUSION: PAI-1 polymorphism is not associated with genesis of IgA nephropathy, but may be a risk factor for the progression of IgA nephropathy in Japanese.

Insulin resistance highly associates with hypertension in IgA nephropathy.

BACKGROUND: Insulin resistance has been reported to induce hypertension. Previous studies described that there was no relationship between insulin resistance and hypertension in patients with chronic renal diseases with mild to moderate renal dysfunction. The aim of the present study is to clarify the relationship between insulin resistance and blood pressure, renal function, histopathological changes and other characteristics in IgA nephropathy (IgAN). METHODS: Eighty-eight IgAN patients were included in this cross-sectional study. Hypertension was diagnosed according to the WHO/ISH criteria. Insulin resistance was evaluated by homeostasis model assessment (HOMA-IR). RESULTS: Male gender, age, body mass index, serum creatinine, urinary protein excretion, triglycerides and HOMA-IR were positively correlated with hypertension. C(Cr), serum albumin and HDL cholesterol were negatively correlated with blood pressure by Spearman's simple correlation test. By logistic multivariate analysis, C(Cr), insulin resistance, age and male gender were significantly correlated with hypertension, independently of all other variables. CONCLUSIONS: Insulin resistance is not directly related to renal dysfunction, but is also independently associated with hypertension in IgAN. Since hypertension is considered as a risk factor for renal disease progression, insulin resistance may be an indirect deteriorating factor for IgAN. To identify and improve insulin resistance may be another therapeutic target in the clinical management of IgAN.