The investigation of killer-cell immunoglobulin-like receptors (KIRs) and their HLA ligands in Iranian patients with myasthenia gravis.

BACKGROUND: Myasthenia gravis (MG) is a disabling disease with the underlying pathophysiology of auto-antibodies attacking the postsynaptic acetylcholine receptors of neuromuscular junctions causing muscle weakness. Natural killer (NK) cells are innate immune cells that play an important regulative role in immune responses. The human killer-cell immunoglobulin-like receptors (KIRs) family is one of the receptors on NK cells that can either activate or inhibit NK cells. This study aimed to assess the possible role of KIR and their human leukocyte antigen (HLA) ligand genes susceptibility to MG in Iranian patients. METHOD: One hundred and sixty-three patients with MG diagnosis based on the presence of clinical symptoms and laboratory tests and 400 healthy volunteers were studied. We used the polymerase chain reaction (PCR) technique for genotyping 15 KIRs and 5 HLA genes. RESULTS: The results demonstrated that there was no significant difference in the frequency of KIR genes and inhibitory KIR genotypes between controls and patients. In MG patients, HLA-C1Asn80 was significantly less frequent than in matched controls. The frequency of HLA genotype number 7 was significantly lower in MG cases, compared to the controls. Analysis of activating KIR genotypes showed that genotype number 10 was significantly less frequent in MG cases than in matched controls. CONCLUSION: Our results suggest that the presence HLA-C1Asn80 might play a protective role against the pathogenesis of MG. The significantly decreased prevalence of one activating KIR genotype and one of the HLA genotypes in MG cases suggest that these genotypes can reduce the risk of MG development. To specifically reveal the impact of KIR and HLA in MG, more studies are required.

COVID outcome in pemphigus: Does rituximab make pemphigus patients susceptible to more severe COVID-19?

BACKGROUND: The COVID-19 pandemic has raised some concerns regarding the management of chronic skin diseases, especially in patients on immunosuppressive therapy including patients with pemphigus vulgaris (PV). Literature review reveals conflicting results about the effect of monoclonal antibodies such as rituximab on clinical outcome of COVID-19. OBJECTIVES: To assess the reciprocal interaction of COVID-19 and pemphigus and the effect of rituximab on prognosis of COVID-19 in patients. METHODS: We set up a retrospective study on adult patients with a confirmed diagnosis of pemphigus vulgaris and a history of COVID-19 with or without symptoms during 2020. RESULTS: Thirty-six adults with pemphigus vulgaris and SARS-CoV-2 infection were included. The SARS-CoV-2 infection was confirmed with positive RT-PCR test results in 31 cases (86.1%) and suspected in the 5 others (13.9%). Gender, total dose of rituximab, number of rituximab cycles, and involvement of head and neck were not associated to duration of COVID-19 symptoms (p values: 0.32, 0.23, 0.84, and 0.51, respectively), severity of disease (hospitalization) (p values: 0.46, 0.39, 0.23, and 0.72, respectively), or the percentage of lung involvement on CT scan (p values: 0.07, 0.36, 0.38, and 0.09, respectively). Regarding the impact of COVID-19 on pemphigus, the majority of patients did not experience any changes in their pemphigus regarding clinical phenotype (100%) or severity (83.3%), but PV was worsened in 6 (16.9%) patients which was controlled with increasing the prednisolone dosage. CONCLUSION: Rituximab appears to be safe with no increased risk of severe form of COVID-19 in patients with pemphigus vulgaris.

Association of Killer Cell Immunoglobulin-like Receptor (KIR) Genes and their HLA Ligands with Susceptibility to Takayasu Arteritis in the Iranian Population.

Takayasu arteritis (TA) is a chronic inflammatory disorder characterized by vascular damage and fibrosis in the intima that commonly occurs in the aorta. In many damaged sites in TA patients, natural killer (NK) cells have been shown to be hyperactivated and produce inflammatory cytokines and toxic components. Killer cell immunoglobulin-like receptors (KIRs) are found on NK cells and interact with human leukocyte antigen (HLA) class I ligands to activate or suppress NK cells. The present study assessed the possible role of KIR and their HLA ligand genes in susceptibility to TA in Iranian patients. This case-control study included 50 TA patients and 50 healthy subjects. DNA was extracted from whole peripheral blood samples, and polymerase chain reaction with sequence-specific primers (PCR-SSP) was performed to recognize the presence or absence of polymorphism in 17 KIR genes and 5 HLA class I ligands in each participant. Among the KIR and HLA genes, a significant decrease was detected in the frequency of 2DS4 (full allele) in TA patients (38%) compared with healthy controls (82%) (OR=0.13, 95% CI=0.05-0.34). However, none of the KIR and HLA genotypes or the interactions between these genes were associated with susceptibility to TA. The KIR2DS4 gene might be involved in the regulation of activation as well as the production of cytotoxic mediators of NK cells in patients with TA.

Retrospective study of gingival involvement in pemphigus: A difficult to treat phenomenon.

Pemphigus is a group of autoimmune diseases characterized by flaccid lesions on the skin and mucous membranes. In pemphigus vulgaris, the most common subtype of pemphigus, lesions might be appeared anywhere on the oral mucosa, mostly in the buccal mucosa. However, the gingiva is a less frequently affected site. Here, we performed a retrospective study at Tehran University of Medical Sciences, covering a two-year period to identify pemphigus patients with active lesions confined to the gingiva. Considering 1787 initially evaluated pemphigus cases, 512 (28.6%) were found to have a history of gingival involvement. Among them, 31 patients had only gingival involvement during their last visit, including 29 (93.5%) women and only two (6.5%) men. The mean of disease duration in this group was 5.29 ± 3.46 years, and they had gingival involvement for a mean of 23.9 ± 19.3 months. Of 28 patients, nine were negative for anti-Dsg3 and 24 were negative for anti-Dsg1. In 24 patients, who received rituximab, the mean pemphigus disease area index specifically for gingiva was 4.76 ± 0.74 at baseline, which had changed to 4.13 ± 0.75 and 3.26 ± 0.63 three and 6 months after rituximab administration, respectively. After 3 months, gingival lesions were either entirely resolved (n = 3), partially resolved (n = 11), remained unchanged (n = 2), or progressed (n = 7). Gingiva-confined presentation of lesions in pemphigus could be non-anti-Dsg1/3 dependent in some patients. Such patients do not respond well to conventional treatments and rituximab therapy. More studies on the pathogenesis of gingiva-confined presentation of pemphigus are required.

Analysis of Killer Cell Immunoglobulin-Like Receptor Genes and Their HLA Ligands in Inflammatory Bowel Diseases.

Genetic studies have illustrated that killer cell immunoglobulin-like receptor (KIR) genes could participate in various autoimmune disorders. We aimed to clarify the role of KIR genes, HLA ligands, HLA-KIR interactions, and their genotypes in inflammatory bowel disease (IBD) susceptibility. The study population was composed of 183 IBD subjects, comprising 100 ulcerative colitis (UC) patients, 83 Crohn's disease (CD) patients, and 274 healthy subjects. Polymerase chain reaction with sequence-specific primers (PCR-SSP) was used to evaluate the absence or presence of the 15 KIR genes, 5 HLA class I ligands, and 2 pseudogenes. We did not find any significant difference in allele frequency of KIRs and pseudogenes between IBD patients and healthy controls. In the case of HLA genes, there was a significant difference in HLA-B-Bw4Thr80 frequency between UC patients and healthy controls (P = 0.03, OR = 0.06, 95%CI = 0.008-0.4). Furthermore, we found a significant difference in HLA-C1Asn80 frequency between CD patients and healthy controls (P = 0.04, OR = 0.49, 95% CI = 0.3-0.8). In the full-array combination of KIR genes, there was no significant frequency difference between UC patients and healthy controls, while two KIR genotypes showed a significant susceptible association with CD. Our data do not support a strong role of NK cells in IBD susceptibility, but it does not rule out a role for KIR variability in IBD patients. However, there are some protective associations such as Bw4 alleles; these associations may be due to the interaction of the alleles to TCRs rather than KIRs.