Could immune cells be associated with nephropathy in Fabry disease patients?

BACKGROUND: In Fabry Disease (FD), although the primary factor initiating kidney damage is glycosphingolipid accumulation, secondary conditions such as increased inflammation and fibrosis may cause this damage to progress. These processes may be induced by immune cells. Therefore, we aimed to investigate the peripheral lymphocyte subgroup analysis of the patients with FD and compare these results with healthy individuals. In addition, we performed T, B, NK, and plasma cell analyses in kidney biopsy materials and compared these kidney biopsy results with the biopsy results of patients whose kidney functions were impaired after 4 years of regular ERT. MATERIALS AND METHODS: 18 FD and 16 healthy individuals were included in the study. T-B lymphocyte and NK-cell populations were determined. We performed kidney biopsies (KBx) on 13 patients with FD prior to ERT. Of these, 4 patients had rebiopsy after 4 years of regular ERT. Immunohistochemical staining was performed to define immune cell infiltration. RESULTS: There was no statistically significant difference in terms of total, helper and cytotoxic T-lymphocyte and CD3-CD16+CD56+ natural killer (NK)-cell count (p = 0.20; p = 0.12; p = 0.76; p = 0.75, respectively).According to KBx findings prior to ERT, all patients had interstitial fibrosis (IF), podocyte vacuoles (PV), and podocyte inclusion (PI), CD3, CD4, CD8, CD16, and CD56 positivity at different levels. None of the patients had CD19, CD20, and CD138 positivity at the first biopsies. When we compared the first and the second KBx results of the two progressors, we also demonstrated that CD3+4+T-cells infiltration remained the same, whereas CD8+T cells, CD16+ and 56+NK-cells infiltration were significantly decreased. In contrast, CD20+B cells and CD138+plasma cell infiltration were significantly increased despite 4 years of ERT (15 fold and sixfold, respectively). The CD20+B and CD138+ plasma cells and IF were positively correlated with proteinuria. CONCLUSIONS: The progression of FD nephropathy and proteinuria is increased despite a long-term ERT. Immune cells, primarily B and plasma cells, might cause these unwanted consequences.

THYROID DISORDERS PREVALENCE IN A COHORT OF KIDNEY TRANSPLANT RECIPIENTS.

CONTEXT: As the life expectancy prolongs, malignancy has become an important issue in renal transplant recipients (RTRs). Thyroid cancer is the most common endocrine malignancy with ongoing increase in incidence all over the world. OBJECTIVE AND DESIGN: This is a cross-sectional study that investigates the thyroid disorders and the prevalence of thyroid nodule and cancer in RTRs. SUBJECTS AND METHODS: 204 RTRs were evaluated for the thyroid diseases with ultrasonography, serum thyroid stimulating hormone, free T4, free T3 levels, anti-thyroglobulin antibody and anti-thyroid peroxidase antibody levels; FNAB was carried if required. RESULTS: 191 patients (94.1%) had normal thyroid function. Subclinical hypothyroidism was diagnosed in 11 patients, subclinical hyperthyroidism in 1 patient and low T3 syndrome in 4 patients. The FNAB was performed in 17 (27.9%) from 61 patients with thyroid nodule. The cytological examination of biopsy materials revealed that 2 (11.8%) nodules were suspicious for malignancy, 13 (76.5%) were benign, and 2 (11.8%) with non diagnostic cytology. Thyroid cancer prevalence was 0.2% in Turkey but we detected that 0.98% of RTRs had thyroid cancer. CONCLUSIONS: Screening the RTRs for thyroid disorders is necessary, so that early diagnosis and appropriate treatment of thyroid disease and cancer may improve the quality of life.

Fabry disease: where are we now?

Fabry disease (FD) is a multisystemic X-linked disorder characterized by the accumulation of lysosomal globotriaosylceramide (Gb3) secondary to decreased activity of α-galactosidase in cells. Generally, males are more severely affected due to the X-linked inheritance pattern of the disease. However, females are asymptomatic or have a less severe pattern of disease. Enzyme replacement therapy (ERT) is the cornerstone of the treatment of FD. At present, there are two forms of ERT that can be applied to FD patients. Novel therapeutic approaches including chaperone therapy, substrate reduction therapy, and gene therapy have been introduced in the era of treatment of FD. In this review, we aimed to discuss the prevalence, clinical and genetic features, pathophysiology, diagnosis, and therapeutic options in FD patients with nephropathy.