Serum IL17 and IL4R RS1805010 genotypes: relationship with rheumatoid arthritis disease activity in Egyptian patients

Rheumatoid arthritis(RA) is characterized by the presence of a relative state of imbalance between pro- and anti-inflammatory cytokines such as Interleukin(IL)17 and IL4, respectively. IL4 is supposed to regulate production of IL17 from T-helper (Th)17 cells. However, this regulatory function might be affected by singlenucleotide polymorphism (SNP) of IL4 receptor (IL4R) gene, rs1805010. The current study aimed to assess serum IL17 level in Egyptian patients with RA according toIL4Rrs1805010 genotypes,and to detect possibleassociations betweenIL17/ IL4R genotypesand clinical status, disease activity as well as effect of treatment. Serum IL17 was assessed by ELISA, and qPCR was used to determine the genotypes of IL4R SNP rs1805010. Serum IL17 was significantly increased in patients’ samples as compared to controls. According to IL4R genotypes, patients with AG and GG genotypes showed significantly higher IL17 levels than control subjects with corresponding genotypes. Within RA group, significantly higher IL17 were found in GG carriers compared to those with AA genotype. The G allele was significantly associated with higherythrocyte sedimentation rate(ESR), increased disease activity score in 28 joints (DAS28), highLarsen score and seropositive rheumatoid factor (RF) as well as C-reactive protein (CRP).Patients with AG and GG genotypes demonstrated significant positive correlations between serum IL17 and DAS28.Meanwhile, serum IL17 levels and Larsen score had significant positive correlation only in GG patients.The use of different treatment regimens did not affect serum IL17 levels significantly in various genotypes. In conclusion, IL17 may be implicated in the pathogenesis of RA, being associated with a higher disease activity parameters, however, its action may be potentiated due to loss of the functional IL4RA allele (rs1805010), particularly in carriers ofthe GG genotype. Furthermore, determining the genetic variants of IL4R rs1805010 may be promising for identification of patients at risk worse prognosis. Key words:Autoimmune disease; pro-inflammatory cytokines;IL4Rgenotypes

Bacterial translocation in an experimental intestinal obstruction model: C-reactive protein reliability? Translocação bacteriana no modelo experimental de obstrução intestinal: A proteína C-reativa é confiável?

BACKGROUND: Bacterial translocation occurs in preseptic conditions such as intestinal obstruction through unclear mechanism. The C-reactive protein is an acute phase reactant and a marker of ischemia. METHODS: 45 albino male rats were divided into 3 groups each 15 rats. GI control, GII simple intestinal-obstruction and GIII strangulated obstruction. Outcome measures were: (1) Bacteriologic count and typing for intestinal contents, intestinal wall, liver, mesenteric lymph nodes and blood (cardiac and portal) (2) Histopathologic: mucosal injury score, inflammatory cell infiltrate in the wall, MLN, liver, (3) Biochemical: serum CRP, IL-10, mucosal stress pattern (glutathione peroxidase-malonyldialdhyde tissue levels). RESULTS: (1) Intestinal obstruction associates with BT precursors (Bact-overgrowth, mucosal-acidosis, immuno-incomptence), (2) Bacterial translocation (frequency and density) was found higher in strangulated I.O, that was mainly enteric (aerobic and anaerobic) and mostly E.coli, (3) The pathogen commonality supports the gut origin hypothesis but the systemic inflammatory response goes with the cytokine generating one. (4) The CRP median values for GI, II, III were 0.5, 6.9, 8.5 mg/L, for BT +ve 8 mg/L and 0.75 mg/L for BT -ve rats. CONCLUSION: Bacterial translocation occurs bi-directional (systemic-portal) in intestinal obstruction and the resultant inflammatory response pathogenesis is mostly 3 hit model. The CRP is a non selective marker of suspected I.O cases. However, it is a reliable marker of BT, BT density and vascular compromise during I.O.<br>OBJETIVO: Translocação bacteriana ocorre em condições pré-sépticas como na obstrução intestinal por mecanismo não esclarecido. A proteína C-reativa é um marcador de ischemia em fase aguda. A proposição é investigar os possíveis efeitos da obstrução intestinal no equilíbrio ecológico microbiano. MÉTODOS: 45 ratos machos albinos foram distribuídos em três grupos de 15 ratos. GI controle, GII obstrução intestinal simples e GIII obstrução estrangulada. As medidas adotadas foram: (1) Contagem bacteriológica do conteúdo intestinal, parede intestinal, fígado, linfonodos mesentéricos e sangue (coração e portal) (2) Avaliação histopatológica da lesão da mucosa, infiltrado celular inflamatório da parede, linfonodos mesentéricos, fígado, (3) Avaliação bioquímica. RESULTADOS: (1) Obstrução intestinal está associada a precursora translocação bacteriana (crescimento bacteriano, acidose da mucosa, imuno-incompetência), (2) Translocação bacteriana (freqüência e densidade) foi maior na obstrução intestinal estrangulada, principalmente entérica (aeróbios e anaeróbios), sobretudo E.coli, (3) A ocorrência comum é de origem intestinal. CONCLUSÃO: A translocação bacteriana na obstrução intestinal é bi-direcional (sistêmica e portal) A proteina C-reativa não é um marcador seletivo na suspeita de obstrução intestinal. Contudo é marcador confiável da translocação bacteriana, na densidade e comprometimento durante a obstrução intestinal