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LINKED CONTENT This article is linked to Al‐Ani et al papers. To view these articles, visit https://doi.org/10.1111/apt.15779 and https://doi.org/10.1111/apt.15940 [ABSTRACT FROM AUTHOR]

The article studies the association of common Mediterranean fever (MEFV) variations with ankylosing spondylitis (AS) in a group of Turkish patients. The study covered 193 patients with AS and 103 matched healthy control subjects genotyped with four MEFV variations and HLA-B27 using genomic DNA. Associations of the variations with the patients' clinical laboratory features are analyzed. The results showed familial Mediterranean fever (FMF)-related MEFV variations are associated with AS and may contribute to AS pathogenesis.

In the title compound, [Zn(C(32)H(40)N(8)S(8))], the Zn(II) ion is coordinated by four N atoms in a slightly distorted square-planar environment. In addition, there is a Zn⋯S contact involving a symmetry-related S atom which, when considered, forms a pseudo-square-pyramidal coordination with respect to the Zn(II) ion. Three of the ethyl groups are disordered over two sites with occupancy ratios of 0.841 (10):0.159 (10), 0.802 (10):0.198 (10) and 0.457 (13):0.543 (13). Weak intra-molecular C-H⋯N and C-H⋯S inter-actions contribute to the stability of the mol-ecular conformation. Inter-molecular C-H⋯S contacts, weak C-H⋯π inter-actions and π-π stacking inter-actions [centroid-centriod distances = 3.832 (4) and 3.850 (5) Å] contribute to the stabilization of the crystal structure.

Objective: Familial Mediterranean fever (FMF) is associated with more than 70 missense mutations in the MEFV gene. The purpose of this study was to investigate the relative expression of messenger RNA (mRNA) for the MEFV gene in peripheral blood leukocytes (PBLs) obtained from patients with FMF during attacks of acute abdominal inflammation as well as during asymptomatic periods., Methods: We studied 16 patients with FMF during an attack of acute peritonitis and 17 otherwise healthy individuals who were undergoing surgery because of acute appendicitis. Blood samples were collected from both groups of patients during both acute inflammatory and asymptomatic periods. Relative levels of MEFV mRNA in PBLs were detected with real-time reverse transcriptase-polymerase chain reaction using LightCycler, with 2 sets of primers for the MEFV gene (exons 7-10 and exons 2-3) and with primers for CIAS1 and PSTPIP1 genes. Expression levels were compared with beta(2)-microglobulin as an internal control., Results: MEFV expression was reduced in FMF patients during asymptomatic periods as compared with the non-FMF controls (P < 0.001). We observed a further decrease in MEFV expression in FMF patients during periods of inflammation (P = 0.01). Reduced levels of MEFV mRNA were also noted during the preoperative period as compared with asymptomatic periods in control patients with acute appendicitis (P = 0.01). CIAS1 expression in PBLs from patients with FMF was also found to be lower than that in the control patients. However, CIAS1 expression did not change with acute inflammation., Conclusion: This study confirmed that reduced expression of the MEFV gene is associated with inflammation and that it may be one of the pathogenic mechanisms of the attacks of inflammation in FMF patients, along with disease-associated variations in pyrin.

Objective: To investigate the effect of infliximab on the frequency of uveitis attacks and the visual prognosis in male patients with Behçet's disease in whom uveitis was resistant to combination therapy with corticosteroids, azathioprine, and cyclosporine., Methods: The study group comprised patients who were receiving combination therapy but experienced at least 2 attacks of posterior uveitis/panuveitis or retinal vasculitis during the 6-month period prior to enrollment. Infliximab infusions (5 mg/kg) were administered at weeks 0, 2, 6, and 14. Weeks 0-22 were defined as the infusion period, and weeks 23-54 were defined as the observation period. Patients continued to receive azathioprine and corticosteroids, but cyclosporine was discontinued after the screening visit. The primary outcome measures were the absence of uveitis attacks during the infusion period (remission), and the absence of uveitis attacks throughout the study period (sustained remission)., Results: Thirteen patients were enrolled in the study. Thirty-two uveitis attacks involving the posterior segment occurred during the previous-treatment period. During the infusion period, 4 patients (30.8%) remained attack-free, and 9 patients had a total of 13 uveitis attacks. Ten of these attacks (76.9%) occurred at either week 14 or week 22. One of 13 patients fulfilled the definition of sustained remission, and the remaining 12 patients had a total of 36 uveitis attacks during the observation period. The mean number of uveitis attacks and daily corticosteroid doses were significantly lower during the infusion period than during the previous-treatment period or the observation period. Although potential visual acuity was regained following infliximab infusion, this beneficial effect was not preserved until week 54. None of the patients experienced a serious adverse event., Conclusion: The results of this trial suggest that infliximab is effective in suppressing the occurrence of uveitis attacks, has a corticosteroid-sparing effect, and has favorable implications for the visual prognosis of patients with resistant Behçet's uveitis.

Objective: Behçet's disease is generally considered to be a multifactorial disease with important genetic and environmental components. A strong association between an HLA class I antigen, HLA-B51, and Behçet's disease has long been known. However, analysis of multicase families has suggested a substantial contribution of non-HLA loci. The aim of this study was to perform a whole-genome linkage analysis for identification of other susceptibility loci for Behçet's disease in multicase families., Methods: The study group comprised a total of 193 individuals (90 male, 103 female) from 28 multicase families of Turkish origin; 83 of the subjects (50 males, 33 females) fulfilled the International Study Group criteria for Behçet's disease. Three hundred ninety-five highly informative microsatellite markers spanning the genome were genotyped using fluorescent polymerase chain reaction primers and a fully automated electrophoresis platform. After the first analysis, 33 additional markers that were located close to the peak linkage areas were genotyped in all individuals. Nonparametric multipoint linkage analysis was carried out using GeneHunter version 2.1 software., Results: Evidence for linkage (P < or = 0.05) was obtained in 16 chromosome regions: 1p36, 4p15, 5q12, 5q23, 6p22-24, 6q16, 6q25-26, 7p21, 10q24, 12p12-13, 12q13, 16q12, 16q21-23, 17p13, 20q12-13, and Xq26-28. After the addition of further markers, the maximum nonparametric linkage score increased from 3.5 to 3.94 at 12p12-13 (D12S77; P = 0.0002) and from 3.07 to 3.70 at 6p22-24 (D6S285; P = 0.0005)., Conclusion: This study is the first systematic genome screen in Behçet's disease and provides evidence of linkage to several non-HLA susceptibility loci in a cohort of Turkish multicase families. This represents the first step toward the identification of novel Behçet's disease susceptibility genes.

Objective: In the Euro-Lupus Nephritis Trial (ELNT), 90 patients with lupus nephritis were randomly assigned to a high-dose intravenous cyclophosphamide (IV CYC) regimen (6 monthly pulses and 2 quarterly pulses with escalating doses) or a low-dose IV CYC regimen (6 pulses of 500 mg given at intervals of 2 weeks), each of which was followed by azathioprine (AZA). After a median followup of 41 months, a difference in efficacy between the 2 regimens was not observed. The present analysis was undertaken to extend the followup and to identify prognostic factors., Methods: Renal function was prospectively assessed quarterly in all 90 patients except 5 who were lost to followup. Survival curves were derived using the Kaplan-Meier method., Results: After a median followup of 73 months, there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen. At long-term followup, 18 patients (8 receiving low-dose and 10 receiving high-dose treatment) had developed permanent renal impairment and were classified as having poor long-term renal outcome. We demonstrated by multivariate analysis that early response to therapy at 6 months (defined as a decrease in serum creatinine level and proteinuria <1 g/24 hours) was the best predictor of good long-term renal outcome., Conclusion: Long-term followup of patients from the ELNT confirms that, in lupus nephritis, a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen. Early response to therapy is predictive of good long-term renal outcome.

Objective: Glomerulonephritis is a severe manifestation of systemic lupus erythematosus (SLE) that is usually treated with an extended course of intravenous (IV) cyclophosphamide (CYC). Given the side effects of this regimen, we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment, followed by azathioprine (AZA) as a remission-maintaining treatment., Methods: In this multicenter, prospective clinical trial (the Euro-Lupus Nephritis Trial [ELNT]), we randomly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen (6 monthly pulses and 2 quarterly pulses; doses increased according to the white blood cell count nadir) or a low-dose IV CYC regimen (6 fortnightly pulses at a fixed dose of 500 mg), each of which was followed by AZA. Intent-to-treat analyses were performed., Results: Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group. Sixteen percent of those in the low-dose group and 20% of those in the high-dose group experienced treatment failure (not statistically significant by Kaplan-Meier analysis). Levels of serum creatinine, albumin, C3, 24-hour urinary protein, and the disease activity scores significantly improved in both groups during the first year of followup. Renal remission was achieved in 71% of the low-dose group and 54% of the high-dose group (not statistically significant). Renal flares were noted in 27% of the low-dose group and 29% of the high-dose group. Although episodes of severe infection were more than twice as frequent in the high-dose group, the difference was not statistically significant., Conclusion: The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis, a remission-inducing regimen of low-dose IV CYC (cumulative dose 3 gm) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen.