Familial Mediterranean fever gene (MEFV) mutations and disease severity in systemic lupus erythematosus (SLE): implications for the role of the E148Q MEFV allele in inflammation.

OBJECTIVE: Observed low prevalence of SLE among familial Mediterranean fever (FMF) patients in several large cohorts suggests a possible protective effect of the MEFV mutations from SLE. In contrast, SLE patient carriers for the common MEFV mutations had rather complex disease expression with an increased frequency of febrile episodes and pleurisy and a decreased renal complication rate. Our aim was to investigate the prevalence of MEFV gene mutations in patients with SLE and their effect on organ involvement in a well-defined group of biopsy-proven SLE nephritis patients. MATERIAL AND METHOD: The prevalence of four MEFV gene mutations (M694V, M680I, V726A and E148Q) was investigated in 114 SLE patients and effect on disease severity was analyzed in patients with biopsy-proven SLE nephritis. RESULTS: None of the SLE patients fulfilled the revised Tel-Hashomer criteria. Fourteen of 114 SLE patients (12.2%) were found to carry at least one MEFV mutation. A single patient in the SLE-Nephritis group was compound heterozygous for M694V/M680I mutations and only one patient in the SLE-Mild group was homozygous for E148Q mutation. Carrier frequency was similar to controls in SLE patients (12.2 vs 18.8%, p = 0.34). After the exclusion of the less penetrant E148Q mutation, re-analysis revealed an association between exon 10 mutations and SLE nephritis (p = 0.050, odds ratio (OR) = 4.16, 95% confidence interval (CI) = 1.04-16.6). Carrier rate for the E148Q mutation decreased in the SLE group (controls vs. SLE = 20/186 vs. 3/114, p = 0.08) and E148Q mutation was absent in SLE nephritis (controls vs. SLE nephritis = 20/186 vs. 0/47, p = 0.016, OR = 11.69, 95% CI = 0.69-197.13). CONCLUSIONS: Carrier rate for the studied MEFV mutations was slightly lower in the SLE group, which is in agreement with previous observations that FMF may confer some protection from SLE. Exon 10 mutations were associated with SLE nephritis after the exclusion of the E148Q mutation. The significance of the E148Q as a disease-causing mutation is controversial, and whether E148Q substitution is a polymorphism generally affecting inflammatory pathways is not addressed in the current literature. In this regard, absence of the E148Q mutation in SLE nephritis may serve as a clue for further investigation into its role as a general modulatory polymorphism for inflammation. This clarification is necessary to conclude whether other more penetrant MEFV gene mutations confer susceptibility to nephritis in SLE.

Ankylosing spondylitis and a diagnostic dilemma: coccydynia.

OBJECTIVES: Coccydynia is defined as pain in or around the tail bone area. The most common cause of coccydynia is either a trauma such as a fall directly on to the coccyx or repetitive minor trauma. The etiology remains obscure in up to 30% of patients. The literature on the contribution of rheumatic diseases to coccydynia is scarce. Our objective was to investigate the prevalence of coccydynia in ankylosing spondylitis (AS) patients. METHODS: One hundred and seven consecutive patients with AS were evaluated for coccydynia were enrolled between January and November 2012 for a cross-sectional analysis. Seventy-four consecutive patients were followed for mechanical back pain as controls and the AS patients were interviewed for the presence of coccydynia. The data collected was evaluated on SPSS® version 11.5 and Microsoft Excel® Programmes. RESULTS: Prevalence of coccydynia in AS (38.3%) was significantly higher than the control group (p<0.0001) in both female and male AS patients (female AS vs. control=40.9% vs. 18.4%, p=0.015 and male AS vs. control=36.5% vs. 8.0%, p=0.005). Both genders were affected equally in the AS group whereas coccydynia was slightly more frequent in female patients in the control group. CONCLUSIONS: Coccydynia is a previously neglected symptom of AS and it is almost three times more common in AS than in non-specific chronic low back pain. Our observation may implicate that inflammatory diseases have a role in the etiology of coccydynia, especially in those without a history of recent or past trauma and coccydynia may be a factor associated with the severity of AS as well.

Propylthiouracil-induced hypothyroidism protects ionizing radiation-induced multiple organ damage in rats.

The objective of this study was to examine the potential radioprotective properties of propylthiouracil (PTU)-induced hypothyroidism against oxidative organ damage induced by irradiation. Sprague-Dawley rats were pre-treated with saline or PTU (10 mg/kg i.p.) for 15 days, and were then exposed to whole-body irradiation (800 cGy). A group of rats were decapitated at 6 h after exposure to irradiation, while another group was followed for 72 h after irradiation, during which saline or PTU injections were repeated once daily. Lung, liver, kidney and ileum samples were obtained for the determination of malondialdehyde (MDA; an index of lipid peroxidation) and glutathione (GSH, an antioxidant) levels, myeloperoxidase activity (MPO; an index of tissue neutrophil accumulation) and collagen contents, while oxidant-induced DNA fragmentation was evaluated in the ileal tissues. All tissues were also examined microscopically and assayed for the production of reactive oxidants using chemiluminescence (CL). Lactate dehydrogenase (LDH), an indicator of tissue damage, and tumour necrosis factor-alpha (TNFalpha) were assayed in serum samples. Irradiation caused a significant decrease in GSH level, which was accompanied by significant increases in MDA levels, MPO activity, CL levels and collagen content of the tissues studied (P<0.05-0.001). Similarly, serum TNFalpha and LDH were elevated in the irradiated rats as compared with the control group. On the other hand, PTU treatment reversed all these biochemical indices, as well as histopathological alterations induced by irradiation. Our results suggested that PTU-induced hypothyroidism reduces oxidative damage in the lung, hepatic, renal and ileal tissues probably due to hypometabolism, which is associated with decreased production of reactive oxygen metabolites and enhancement of antioxidant mechanisms.