Ezzeddine Abderrahim

Human platelet antigens polymorphisms and susceptibility of thrombosis in hemodialysis patients

To investigate the association between the polymorphisms of human platelet antigen (HPA)‐1,2,3,4,5 and susceptibility to develop thrombosis accident in arteriovenous fistula (AVF), genomic DNA of 112 hemodialysis (HD) patients and 100 healthy blood donors were genotyped by PCR‐SSP. The patients were classified into 2 groups: G1 included 54 HD patients presented at least one thrombotic episode on the level of the AVF, and G2 included 58 HD patients without any episode of thrombosis. The allelic frequencies of HPA‐1, 2, 3, and 5 among patients and controls did not reveal significant differences. However, the HPA‐4b allele was significantly more frequent in G1 than in controls or in G2 patients (23.1% vs. 11.5% and 0.9%, respectively), p<0.01 and p<0.001. The genotype distribution of HPA‐4 polymorphism reveals that the HPA‐4a4b genotype was more frequent in G1 patients (23/54: 42.6%) than in all HD patients (25/112: 22.3%) or in G2 patients (1/58: 1.72%) (p<0.001, odds ratio: 45.6). Among 24 HD patients with HPA‐4a4b genotype, 23 (96%) developed at least 1 or more thrombotic episode on the level of their AVF. However, 30 patients (34.5%) among 87 HD patients with HPA‐4a4a genotype presented thrombotic episode (p<0.001). These results reveal a significant association between HPA‐4a4b and thrombosis, and it is likely that HPA polymorphisms could be useful markers for potential risk of thrombosis in hemodialysis.

Evaluation of CTLA-4, CD28 and CD86 Genes Polymorphisms in Acute Renal Allograft Rejection among Tunisian Patients

Kidney transplantation is the preferred therapy for most patients with end-stage renal disease (Sui et al., 2008; Turgeon et al., 2009). Transplantation improves both quality of life and survival (Chavez et al., 2008). Unfortunately, the rate of renal allograft rejection remains important. With the aim of reducing the level of transplantation failure, several researches were achieved to elucidate the immunological mechanisms involved in this process. Thus, it was well established that allograft rejection is an immune response strongly depending on T cells proliferation. In fact, T lymphocytes play a crucial role in the initiation and the regulation of the adaptive immune response to foreign or native antigen (Vincenti, 2008). Herein, we focused on the costimulatory molecules: CTLA-4 and CD28: two receptors of T lymphocytes, and CD86: their common ligand on the antigen presenting cells (APC).

Pronostic rénal de la néphropathie des vascularites à IgA de l’adulte: étude monocentrique, à propos de 25 cas

IgA vasculitis nephritis affects the prognosis of this disease in adult patients. This study aimed to examine the clinical characteristics of this renal involvement in adults and to identify factors influencing renal prognosis. We conducted a retrospective monocentric study of patients with histologically confirmed IgA vasculitis nephritis (rheumatoid purpura) (EULAR classification criteria) with renal involvement classified according to Pillebout classification. We analyzed renal survival and identified the factors influencing renal prognosis. Twenty-five patients were included (sex ratio M/F = 2.57), their average age at diagnosis of rheumatoid purpura was 35,76 years. Purpura was diagnosed in 100% of cases, with articular involvement in 28% of cases. Renal failure was identified in 44% of cases. The most common histological classification was IgA vasculitis nephritis (class II). Clinical remission was observed in 44% of cases and an evolution toward chronic renal failure (end-stage renal disease) in 36% of cases. Renal survival at 195 months was 57%. The identified prognostic factors were digestive involvement (p = 0.022), early renal failure (p = 0.0004), glomerular classification (P=0,001) and the severity of the histological lesions, renin-angiotensin system blocker treatment (p = 0.01) and plasma exchanges (p = 0.03). Our study shows that renal involvement during IgA vasculites can be relatively severe with poor renal prognosis. The identification of clinical and histological prognostic factors may be useful as guidance for the development of prospective therapeutic studies.La néphropathie de la vascularite à IgA conditionne le pronostic de cette affection chez l’adulte. Le but de notre étude était d’étudier les caractéristiques cliniques de cette atteinte rénale chez l’adulte et d’identifier les facteurs de pronostic rénal. Il s’agit d’une étude monocentrique rétrospective portant sur les patients ayant une vascularite à IgA (purpura rhumatoïde) (critères de l’EULAR) avec une atteinte rénale prouvée histologiquement et classée selon la classification de Pillebout. Nous avons analysé la survie rénale et identifier les facteurs de pronostic rénal. Vingt cinq patients ont été inclus (genre ratio M/F = 2,57) d’âge moyen au diagnostic du purpura rhumatoïde de 35,76 ans. Un purpura était présent dans 100% des cas avec une atteinte articulaire dans 28%. Une insuffisance rénale était présente dans 44% des cas. La classification histologique la plus fréquente était la classe II. Une rémission clinique a été observée dans 44% des cas et une évolution vers le stade terminal de l’insuffisance rénale chronique dans 36% des cas. La survie rénale à 195 mois était de 57%. Les facteurs pronostiques identifiés étaient l’atteinte digestive (p = 0,022), l’insuffisance rénale initiale (p = 0,0004), la classification glomérulaire (p = 0001) et la sévérité des lésions histologiques, le traitement par bloqueurs du système rénine angiotensine (p = 0,01) et les échanges plasmatiques (p = 0,03). Notre étude montre que l’atteinte rénale au cours des vascularites à IgA peut être relativement sévère avec un mauvais pronostic rénal. L’identification des facteurs pronostiques cliniques et histologiques pourrait guider l’élaboration d’études thérapeutiques prospectives.

The role of IL‐23/IL‐17 axis in human kidney allograft rejection

Th17 cell subset has been implicated in autoimmune diseases, tumor immunity and, transplant rejection. In order to investigate the role of IL‐17/IL‐23 pathway in allograft outcome, intragraft expression of IL‐17 mRNA and single nucleotide polymorphisms (SNPs) of IL‐17A, IL‐17F, IL‐17RC, and IL23R genes were evaluated with a quantification of IL‐17A, IL‐17F, and IL‐23 plasma levels. This study revealed that recipients with acute rejection (AR) had a significant increase in IL‐17A mRNA expression levels after transplantation compared to controls (P = 0.037). Moreover, IL‐17A plasma levels were significantly higher in AR group; pretransplantation (Day–1 [D–1]): P = 0.00022 and posttransplantation (Day 7 [D7]): P < 10–14. IL‐17F and IL‐23 plasma levels were significantly higher in AR at D7 only (47.86 vs. 22.99 pg/ml; and 33.82 vs. 18.811 pg/ml; P = 0.015 and P < 10–17, respectively). Using receiver‐operating characteristic curves, D7 IL‐17A and IL‐23 plasma levels exhibited excellent sensitivities and specificities for predicting AR. Genetic study revealed no association between IL‐17A, IL‐17F, IL‐17RC, and IL23R studied SNPs and AR. Nevertheless, a significant improvement of graft survival was found in kidney transplant recipients carrying IL‐17F‐rs763780*A/A, IL‐17RC*G/G, and *G/A genotypes. Besides, IL‐17A mRNA levels were significantly higher in patients carrying the IL‐23R*G/G genotype comparatively to those with *G/A genotype. Based on these findings, significant increase of IL‐17A mRNA and protein levels in AR recipients that are genetically controlled highlights the role of this cytokine that can be a useful clinical biomarker to predict early acute renal allograft rejection.

Light chain nephropathy.

Light chain deposition disease (LCDD) is characterized by the tissue deposition of monotypic immunoglobulin light chains of either kappa or lambda isotype. It is the archetypal systemic disease that is most frequently diagnosed on a kidney biopsy, although the deposits may involve several other organs. This brief review focuses on the clinicopathological features of LCDD-associated nephropathy with an emphasis on the diagnostic and therapeutic difficulties related to this elusive condition.