NLRP3 inflammasome (rs10754558) gene polymorphism in patients with atopic dermatitis.

The nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome is a high molecular weight protein complex that has been linked to a variety of allergic and inflammatory disorders in humans, including atopic dermatitis (AD). Polymorphisms in NLRP3 genes could lead to immune dysregulation. This case-control study aimed to assess the association between NLRP3 inflammasome (rs10754558) gene polymorphism in AD and the incidence and severity of the disease. We included 62 subjects in each of the AD and control groups. Serum total IgE levels and NLRP3 inflammasome (rs10754558) gene polymorphism were assessed and compared between the two study groups and among the AD group as arranged by disease severity. The AD group showed significantly higher levels of serum total IgE compared to controls (p˂0.001). Serum IgE levels were also significantly associated with AD severity. The (rs10754558) G allele was significantly predominant among AD participants (OR: 2.33; 95% CI: 1.1 -4.92) and 51.6% of the AD group was carriers of the GG genotype. Moreover, there was a substantial correlation between NLRP3 (rs10754558) G allele and AD score index for disease severity (OR: 7.17; 95% CI: 1.47 - 35.7). In conclusion, NLRP3 inflammasome (rs10754558) gene polymorphism G allele could be an important factor in the predisposition and exacerbation of AD.

Pollen sensitization among Egyptian patients with respiratory allergic diseases.

Pollen is responsible for seasonal allergies, such as allergic rhino-conjunctivitis (AR), and has become a growing public health concern. Climate change affects the range of allergenic species as well as the timing and length of the pollen season. In Egypt, data on pollinosis are scarce. This study aimed to identify the most prevalent pollen causing allergies among Egyptian patients with respiratory allergies. A total of 200 patients with respiratory allergic diseases, allergic rhinitis and/or bronchial asthma (BA), were included. Medical history taking and physical examinations were conducted on each patient. Complete blood count (CBC), total immunoglobulin E (IgE) determination, spirometry, specific IgE, and skin prick tests (SPTs) for common aeroallergens and food were performed. Of the 200 patients, 106 (53%) were females. The age of study subjects ranged 16-66 years (mean ± SD, 34.42 ± 13.0), and 65% were living in urban areas. Grass pollen, mainly from Timothy grass and maize, were the most prevalent allergens (28.5%). Timothy grass was the most common type of pollen in patients with AR (28.3 %). Elder pollen was more prevalent among asthmatic patients (P = 0.004). Bermuda grass was statistically more prevalent in rural than in urban areas (P = 0.008). Maize was linked to uncontrolled BA, whereas Timothy grass was the most prevalent among patients with moderate/severe AR. Forty-three patients had oral allergy syndrome; oranges and tomatoes were the most cross-reactive food allergies (12% and 11.5%, respectively). Exacerbation of allergic symptoms was noted during January, December, March, and June. In conclusion, pollen plays a substantial role in affecting patients with respiratory allergies in Egypt. Grass pollen is the most prevalent type of pollen, especially in urban areas.

Stem cell transplantation for induction of remission in medically refractory Crohn's disease.

BACKGROUND: Crohn's disease (CD) is an inflammatory bowel disease that causes inflammation and stricture, of any part of the mucosa and the gut wall. It forms skip lesions, sparing the areas in between the affected parts of the gastrointestinal tract. Crohn's disease could have one of three complications; fistula, intestinal obstruction due to stricture, or gastrointestinal inflammation presenting as severe diarrhoea. Stem cell therapy (SCT) is an innovative treatment that has been recently used in CD. The exact role of SCT in CD is still unclear. Stem cells modify the immunity of the patients or act as a "reset tool" for the immune system as in the case of systemically-injected stem cells, or regenerate the affected area of necrotic and inflammatory tissue as in the case of local injection into the lesion. Stem cells are a wide variety of cells including pluripotent stem cells or differentiated stem cells. The hazards range from rejection to symptomatic manifestations as fever or increase infection.  OBJECTIVES: The objective of this Cochrane systematic review is to assess the effects of stem cell transplantation compared to standard of care alone or with placebo on efficacy and safety outcomes in patients with refractory CD. SEARCH METHODS: We searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and clinical trial registries (Clinicaltrials.gov, World Health Organization-International Clinical Trials Registry Platform WHO ICTRP) from inception to 19 March 2021, without any language, publication year, or publication status restrictions. In addition, we searched references of included studies and review articles for further references. An update of the published studies was done during the writing of the review. SELECTION CRITERIA: We included only randomised controlled trials (RCTs) that assessed the effectiveness and safety of SCT in refractory CD versus standard care alone (control) or with placebo. DATA COLLECTION AND ANALYSIS: Two review authors (SEN and SFA) independently screened the studies retrieved from the search results for inclusion, extracted data and assessed the risk of bias. Any disagreement was resolved through a consensus between the authors. We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We conducted our search on 19 March 2021 and identified 639 records. We added two records by a manual search of the published reviews on the topic to a total of 641 records. The Covidence program removed 125 duplicates making a total of 516 reports. Two review authors (SEN and SFA) screened titles and abstracts and excluded 451 records with the remaining 65 for full-text records screened independently by the two authors; only 18 studies were considered for inclusion.  We included seven RCTs with a total of 442 participants for the meta-analysis. The intervention group included 234 patients, and the control group included 208 patients. Nine trials are ongoing and, two abstracts are awaiting classification. All patients in the control and intervention groups received the standard therapy for CD. Only three studies used blinding methods for the control group in the form of a placebo, with one study of the three stated that the blinding method was inefficient. The patients and personnel were aware of the intervention in the rest of the four studies as they were open-label trials. However, the effect of unblinding was balanced by the low risk of detection bias in five of the included studies. The evidence is uncertain about the effect of SCT on achieving clinical remission as compared to control/placebo (risk ratio (RR) 1.88, 95% Confidence Interval (CI) 0.80 to 4.41; 3 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT on achieving Crohn's Disease Activity Index (CDAI) <150 at 24 weeks compared to control (RR1.02 95% CI 0.67 to 1.56; 4 studies; very-low certainty evidence). SCT is likely to achieve fistula closure as compared to the control/placebo both in the short term (RR 1.48, 95% CI 1.12 to 1.96); low-certainty evidence) and in the long term (RR 1.42, 95% CI 1.09 to 1.87; 4 studies; low-certainty evidence) follow-up. The evidence is very uncertain about the effect of SCT to cause no difference in the number of total adverse events as compared to the control/placebo (RR 0.99, 95% CI [0.88 to  1.13); 4 studies; very-low-certainty evidence). However, SCT is likely to increase the number of serious adverse events as compared to the control/placebo (RR 1.22, 95% CI 0.88 to 1.67; 7 studies; low-certainty evidence). The evidence is very uncertain about the effect of SCT to decrease the withdrawal due to adverse events as compared to the control/placebo (RR 0.78, 95% CI 0.32 to 1.89; 3 studies; very-low certainty evidence). Funding by pharmaceutical companies was found in three studies, with one including more than 50% of our studied population. AUTHORS' CONCLUSIONS: SCT shows an uncertain effect on clinical remission with low certainty of evidence. SCT shows an uncertain effect on CDAI score to reach <150 after 24 weeks of treatment, with very low certainty evidence. SCT shows beneficial effects on fistula-closure during short and long-term follow-up with low-certainty evidence in both outcomes. There was no change in the total number of adverse events with SCT as compared to control, with very low certainty evidence. While there was a moderate effect on increasing the number of serious adverse events in the SCT group, as compared to the control with low-certainty evidence. Withdrawal due to adverse events was slightly higher in the control group with very low certainty evidence. All the participants were refractory to standard medical treatment, but the number of participants was small, this may limit the generalizability of the results. Further research is needed for validation. More objective outcomes are needed in the assessment of stem cell effectiveness in the treatment of Crohn's disease, especially the intestinal CD subtype; with standardization of the dose, methods of stem cell preparation, route of administration, and inclusion criteria to the studies to achieve clear results.

Anti-tubulin-alpha-1c antibody as a marker of value in Behçet syndrome.

BACKGROUND: Behçet's syndrome (BS) is a multi-systemic vasculitis characterized by recurrent oral ulcers, genital ulcers, ocular lesions, and other systemic manifestations. As there is no laboratory diagnostics of BS, the diagnosis is mainly clinical. OBJECTIVE: To investigate the utility of the autoantibody against tubulin-α-1c in diagnosis of BS and its clinical significance. METHODS: Sixty BS patients and sixty healthy controls were enrolled in this study. We assessed all patients by Behçet disease current activity form (BDCAF), routine laboratory investigations, and immunological markers (ANA, anti-DNA, ANCA). Anti-endothelial cell antibodies (AECA) and anti-tubulin-alpha-1c antibodies were performed for all participants. RESULTS: Regarding duration of illness, Birmingham Vasculitis Activity Score (BVAS), and BDCAF, the mean value was 4.77 ± 4.239, 19.80 ± 10.020, and 9.52 ± 5.476, respectively. On comparing laboratory investigations, there was only significant increase in anti-tubulin-alpha-1c antibody in BS patients compared to healthy controls. Regarding AECA, there was no any significant correlation except with CRP. Anti-tubulin-alpha-1c detected significant direct correlation with the presence of posterior uveitis, panuveitis, and venous thrombosis as well as BVAS, C4, and protein/creatinine ratio. Regarding diagnostic performance of both AECA and anti-tubulin-alpha-1c, the cutoff value of AECA for diagnosis was 27.250, with sensitivity and specificity of 93.3% and 96.7%, respectively. The cutoff value of the anti-tubulin-alpha-1c for diagnosis was 22.300, with sensitivity and specificity of 100% and 96.7% respectively. CONCLUSION: Anti-tubulin-α-1c antibodies are of diagnostic value in BS and are indicative of activity with 100% sensitivity and 96.7% specificity. Key Points • There is lack of specific laboratory, radiological, or histological diagnostics for Behcet syndrome. • We aimed to evaluate the significance of tubulin-α-1c autoantibody in diagnosis of Behcet syndrome. • There is elevation of tubulin-α-1c autoantibody with sensitivity and specificity of 100% and 96.7%, respectively.