High prevalence of spondyloarthritis and ankylosing spondylitis among familial Mediterranean fever patients and their first-degree relatives: further evidence for the connection

Introduction

Familial Mediterranean fever (FMF) is an auto-inflammatory disease characterized by recurrent attacks of fever and serositis. Limited data suggest that the prevalence of sacroiliitis is increased in patients with FMF. In our present study, we assessed the prevalence of spondyloarthritis (SpA), including ankylosing spondylitis (AS), among a cohort of FMF patients and their unaffected first-degree relatives (FDRs).

Methods

The current study cohort comprised a consecutive group of 201 unrelated patients with FMF and 319 FDRs (≥ 16 years old). These subjects were examined according to a standard protocol.

Results

A total of 157 FMF patients (78.1%) and 233 (73%) unaffected FDRs reported back pain. Fifteen FMF patients (7.5%) and nine unaffected FDRs fulfilled the modified New York (mNY) criteria for AS. One additional FDR with AS was identified after review of the medical records. None of the FMF patients with AS was HLA-B27 positive. The allele frequency of M694V among the FMF patients with radiographic sacroiliitis was significantly higher in comparison with those without sacroiliitis (OR 4.3). When compared with the general population, the risk ratios for SpA and AS among the FDRs of our FMF patients were 3.3 (95% CI; 2.0 to 5.5) and for AS 2.9 (95% CI; 1.3 to 6.4), respectively.

Conclusions

Our study suggests that a) factors other than HLA-B27 play a role in the association of FMF and SpA/AS; b) MEFV gene variations may be one of the geographic/region-specific potential pathogenetic links between these two disorders in the Turkish population.     

Q192R polymorphism in the PON1 gene and nasal polyp in a Turkish population

The pathogenesis of nasal polyps is not completely understood. Oxidative damage contributes to polyp formation in the nasal mucosa. The paraoxonase 1 (PON1) enzyme is an important liver enzyme with high antioxidant activity. In this study, we investigated the correlation between Q192R genotypic polymorphism of the PON1 enzyme and nasal‐polyp disease. The study examined 62 nasal‐polyp patients and 88 controls. PON1 Q192R polymorphism was determined using polymerase chain reaction‐restriction fragment length polymorphism. The genotype distribution of the PON1 gene was significantly different between nasal‐polyp patients (QQ = 69.35%, QR = 25.81%, RR = 4.83%) and healthy controls (QQ = 52.27%, QR = 44.31%, RR = 3.40%). Our results suggest that the PON1 QQ genotype (odds ratio [OR] = 2.066, P = .036) is associated with a higher risk of developing the nasal‐polyp disease while QR genotype (OR = 0.437, P = .021) showed a lower risk.     

Coiled‐coil registry shifts in the F684I mutant of Bicaudal D result in cargo‐independent activation of dynein motility

The dynein adaptor Drosophila Bicaudal D (BicD) is auto‐inhibited and activates dynein motility only after cargo is bound, but the underlying mechanism is elusive. In contrast, we show that the full‐length BicD/F684I mutant activates dynein processivity even in the absence of cargo. Our X‐ray structure of the C‐terminal domain of the BicD/F684I mutant reveals a coiled‐coil registry shift; in the N‐terminal region, the two helices of the homodimer are aligned, whereas they are vertically shifted in the wild‐type. One chain is partially disordered and this structural flexibility is confirmed by computations, which reveal that the mutant transitions back and forth between the two registries. We propose that a coiled‐coil registry shift upon cargo‐binding activates BicD for dynein recruitment. Moreover, the human homolog BicD2/F743I exhibits diminished binding of cargo adaptor Nup358, implying that a coiled‐coil registry shift may be a mechanism to modulate cargo selection for BicD2‐dependent transport pathways.     

Effects of the mTOR and AKT genes polymorphisms on systemic lupus erythematosus risk

Molecular Biology Reports - The systemic lupus erythematosus (SLE) is an autoimmune disease, leading to inflammatory response and systemic consequences. The mammalian target of rapamycin (mTOR) is...     

Effects of Lactobacillus acidophilus and Bifidobacterium bifidum Probiotics on the Expression of MicroRNAs 135b, 26b, 18a and 155, and Their Involving Genes in Mice Colon Cancer

Probiotics and Antimicrobial Proteins - A wide range of sources supports that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora. In this case, it...     

Structure of complex III with bound cytochrome c in reduced state and definition of a minimal core interface for electron transfer

In cellular respiration, cytochrome c transfers electrons from cytochrome bc(1) complex (complex III) to cytochrome c oxidase by transiently binding to the membrane proteins. Here, we report the structure of isoform-1 cytochrome c bound to cytochrome bc(1) complex at 1.9 A resolution in reduced state. The dimer structure is asymmetric. Monovalent cytochrome c binding is correlated with conformational changes of the Rieske head domain and subunit QCR6p and with a higher number of interfacial water molecules bound to cytochrome c(1). Pronounced hydration and a "mobility mismatch" at the interface with disordered charged residues on the cytochrome c side are favorable for transient binding. Within the hydrophobic interface, a minimal core was identified by comparison with the novel structure of the complex with bound isoform-2 cytochrome c. Four core interactions encircle the heme cofactors surrounded by variable interactions. The core interface may be a feature to gain specificity for formation of the reactive complex.     

Comparison of culture and PCR for the detection of Brucella melitensis in blood and lymphoid tissues of serologically positive and negative slaughtered sheep

Aims: To compare the culture and PCR methods for detection of Brucella melitensis in blood and lymphoid tissue samples obtained from slaughtered sheep (n = 162) testing positive/negative in serological tests (Rose Bengal test and serum agglutination test). Methods and Results: Of 162 sheep examined, 45 were positive and 117 negative in serological tests. A PCR assay based on a pair of Br. melitensis‐specific primers was used to detect DNA in blood and lymphoid tissue. Brucella melitensis was isolated from 1·2% (2/162) and 17·2% (28/162) of the blood and lymphoid tissue samples respectively. Positive PCR products with a molecular size of 731 bp were obtained from 27·7% (45/162) of blood and 29·0% (47/162) of lymphoid tissue samples. Conclusions: The species‐specific PCR assay detected a higher number of Br. melitensis DNA both from serologically positive (P < 0·01 in blood PCR, P < 0·001 in tissue PCR) and serologically negative (P < 0·001 in both blood PCR and tissue PCR) sheep compared with classical bacteriological culture methods. Significance and Impact of the Study: The results emphasize the importance of using more than one type of diagnostic technique for the detection of animals positive for brucellosis, especially with epidemiological purposes.