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Behçet's disease (BD) is a multisystemic inflammatory disease of unknown cause. Beta defensins (β-defensins) are endogenous antimicrobial peptides that have the ability to kill or inactivate a wide spectrum of bacteria and fungi by changing their membranes stability. It also plays a significant role in inflammation owing to its chemotactic activity for T cells and immature dendritic cells. To explore whether β-defensins might be involved in BD pathogenesis, serum human β-defensin-1 (hBD-1) and defensin-β-1 (DEFB1)-20 G/A gene polymorphism were assessed in patients with BD. The study included 40 BD patients and 40 matched controls. Serum hBD-1 was assessed by enzyme-linked immunosorbent assay (ELISA) and the -20G/A genotypes (rs11362) were determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) analysis. The mean age of patients was 33.5 ± 10.8 years. They were 32 males and 8 females (M:F 4:1). Disease duration was 8.5 ± 7.3 years. In patients, the median serum hBD-1 concentration was 295.5 pg/ml (27.6–1776.6 pg/ml) and was significantly higher than in the control (median 129.6 pg/ml; 23.7–986.3 pg/ml) (p < 0.001). Serum hBD-1 significantly correlated with C-reactive protein (r = 0.85, p = 0.001) and platelets (r = 0.4, p = 0.012). No significant difference was found between patients and control regarding genotyping of -20G/A DEFB1 (rs11362). Skin manifestations were significantly higher among patients with GA genotype 18/23 (78.2 %) than patients with AA genotype 7/16 (43.8 %)(p = 0.027). However, there was no association between serum hBD-1 and −20A/G polymorphism. The hBD-1 is implicated in the pathogenesis of BD and may be a possible therapeutic target. [ABSTRACT FROM AUTHOR]

Cernunnos deficiency is a rare genetic disorder characterized by immunodeficiency, microcephaly, growth retardation, bird-like facies, sensitivity to ionizing radiation, few autoimmune manifestations, premature aging of hematopoietic stem cells at an early age, and occasional myeloproliferative disease. Herein we present five Egyptian Cernunnos patients from 3 different families. We describe the patients' clinical phenotypes, their immunological profile as well as genetic results. Sequence analysis revealed three different mutations in the NHEJ1 gene: a nonsense variant c.532C > T; p.(Arg178Ter), an intronic variant c.178-1G > A and a frameshift insertion variant c.233dup; p.(Asn78LysfsTer14). In conclusion, Cernunnos deficiency can have a wide range of clinical features. The characteristic immune profile including a decrease in recent thymic emigrants and naive T cells, markedly elevated memory T cells together with normal to high IgM, and a decrease in IgG and IgA. This immune profile is highly suggestive of Cernunnos deficiency in T-B-NK + SCID patients especially surviving for older ages. • This is the first Egyptian report of patients with mutations in NHEJ1 gene. • c.532C > T; p.(Arg178Ter), c.178-1G > A and c.233dup had been identified in NHEJ1 gene. • Cernunnos deficiency can have a wide range of clinical features. • Suspicion is raised in SCID with elevated memory and decrease naïve T cells. • Presence of BM aplasia and absence of malignancies are disease hallmarks. [ABSTRACT FROM AUTHOR]