Arkadiusz Chlebicki

Does the KIR2DS5 Gene Protect from Some Human Diseases

Background KIR2DS5 gene encodes an activating natural killer cell receptor whose ligand is not known. It was recently reported to affect the outcome of hematopoietic stem cell transplantation. Methodology/Principal Findings In our studies on KIR2DS5 gene associations with human diseases, we compared the frequencies of this gene in patients and relevant controls. Typing for KIR2DS5 gene was performed by either individual or multiplex polymerase chain reactions which, when compared in the same samples, gave concordant results. We noted an apparently protective effect of KIR2DS5 gene presence in several clinical conditions, but not in others. Namely, this effect was observed in ankylosing spondylitis (p = 0.003, odds ratio [OR] = 0.47, confidence interval [CI] = 0.28–0.79), endometriosis (p = 0.03, OR = 0.25, CI = 0.07–0.82) and acute rejection of kidney graft (p = 0.0056, OR = 0.44, CI = 0.24–0.80), but not in non-small-cell lung carcinoma, rheumatoid arthritis, spontaneous abortion, or leukemia (all p>0.05). In addition, the simultaneous presence of KIR2DS5 gene and HLA-C C1 allotype exhibited an even stronger protective effect on ankylosing spondylitis (p = 0.0003, OR = 0.35, CI = 0.19–0.65), whereas a lack of KIR2DS5 and the presence of the HLA-C C2 allotype was associated with ankylosing spondylitis (p = 0.0017, OR = 1.92, CI = 1.28–2.89), whereas a lack of KIR2DS5 and presence of C1 allotype was associated with rheumatoid arthritis (p = 0.005, OR = 1.47, CI = 1.13–1.92). The presence of both KIR2DS5 and C1 seemed to protect from acute kidney graft rejection (p = 0.017, OR = 0.47, CI = 0.25–0.89), whereas lack of KIR2DS5 and presence of C2 seemed to favor rejection (p = 0.0015, OR = 2.13, CI = 1.34–3.37). Conclusions/Significance Our results suggest that KIR2DS5 may protect from endometriosis, ankylosing spondylitis, and acute rejection of kidney graft.

Cytokine profiles in axial spondyloarthritis.

Objectives Current studies concentrate on the cytokine network and its role in the pathogenesis of spondyloarthritis (SpA). In this study, we analyzed whether the serum cytokine profile (interleukins: IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33) correlates with demographic data, clinical manifestations, disease activity and treatment outcome in a group of patients with axial spondyloarthritis. Material and methods Forty-nine patients with an established diagnosis of axial spondyloarthritis (aSpA) and 19 healthy volunteers as controls were enrolled in the study. Clinical evaluation included patients medical history, 44 joint count, back pain intensity and global disease activity in the preceding week (VAS), the duration of morning stiffness and blood tests. Disease activity was assessed using BASDAI and ASDAS-CRP. Serum concentration of IL-10, IL-11, IL-12, IL-15, IL-17, IL-23 and IL-33 was determined. Results In patients with aSpA, elevated serum concentration of IL-10, IL-15, IL-17 and IL-23 was detected. In the aSpA group we detected higher values of serum concentration of IL-23 and IL-33 in the subgroup with anterior uveitis (83.1 ±184.0 pg/ml vs. 14.0 ±17.1 pg/ml, p < 0.0001 and 45.5 ±71.9 pg/ml vs. 18.4 ±14.3 pg/ml, p < 0.0001, respectively). Additionally, in the subgroup with peripheral arthritis, elevation of serum concentration of IL-12 (249.3 ±246.9 pg/ml vs. 99.9 ±105.9 pg/ml, p = 0.0001) was detected. Patients with preradiological SpA had higher serum concentration of IL-17 than patients with established diagnosis of AS (6.37 ±8.50 pg/ml vs. 2.04 ±2.98 pg/ml, p = 0.0295). No differences in serum concentration of analyzed cytokines were found between the subgroup with low to moderate disease activity and the subgroup with high to very high disease activity. Conclusions We report that in aSpA patients, compared to controls, elevated serum concentrations of IL-10, IL-15, IL-17 and IL-23 were observed. Some cytokines may predispose to a more severe course of aSpA.

The variety of clinical presentations in IgG4-related disease in Rheumatology

IgG4-related disease (IgG4-RD) belongs to the group of rare diseases in which the identification of the characteristic histology and immunohistochemistry provides with the gold standard in the diagnosis. The variable organ dysfunction reflects the clinical presentation. The examples of different IgG4-RD presentations in the Rheumatology Unit were discussed in this article. The spectrum of IgG4-RD is wide-ranging and manifested in one or more organs synchronously or metachronously. In the presented article, we described five different cases of IgG4-RD. Four cases were reaffirmed in the histopathological assessment. The clinical and laboratory findings were analyzed and the assigned therapy was discussed. According to our experience, the diagnosis of IgG4-RD requires the careful clinicopathological correlation. The diagnosis relies on the coexistence of various clinical, laboratory, radiological, and histopathological findings, although none of them is pathognomonic itself. The time needed for the diagnosis and variety of clinical forms of IgG4-RD shows that there is need of the cooperation among many specialists for the better and earlier recognition of the disease.

Disease activity in axial spondyloarthritis after discontinuation of TNF inhibitors therapy

Objective Use of tumour necrosis factor inhibitors (TNFi) has proved to be an important step forward in the treatment of axial spondyloarthritis (axSpA), but the duration of the therapy as well as the management in case of low disease activity (LDA) or remission are not clearly established. Currently, the identification of potential predictors associated with the treatment discontinuation is the basic purpose of many clinical studies. The aim of this study was to analyze the influence of the discontinuation of TNFi therapy on the disease activity in patients with low disease activity. Material and methods The study included 65 patients; 47 of patients (72%) were treated with etanercept, 16 (2%) with adalimumab and 2 (3%) with infliximab. Results The mean age of the patients was 45 years, the mean BASDAI score was 6.8 and VAS for low back pain was 76 mm at baseline. 54 patients with axSpA (83%) achieved LDA after 9 months of anti-TNF therapy. During follow-up 40 patients (74% of patients with LDA) had an increase of the disease activity after mean 14 weeks and needed to restart the treatment with TNFi. After restart of the therapy LDA was regained in all patients after mean 7 weeks. 11 patients (17%) have never achieved LDA and 14 patients (22%) had LDA longer than 6 months without relapse. At baseline higher levels of CRP and ESR were observed in patients with relapse of the disease at the end of treatment and with LDA shorter than 6 months. Conclusions Changes in the values of disease activity indicators (CRP, ESR) correlated with more stable response to TNFi therapy. Over 50% of patients who were treated with TNFi needed to restart the therapy. Treatment resumption allowed to regain a good clinical effect among affected patients.

Systemic Lupus Erythematosus Induced by Autoimmune/ Inflammatory Syndrome Induced by Adjuvants. Is it Possible? Long-Term Follow-up and Literature Review

©2018 Turkish League Against Rheumatism. All rights reserved. There are reports in the literature describing a relationship between the use of adjuvants and development of autoimmune diseases.1 In this article, we present a case of 37-year-old female patient who was hospitalized in 2010 due to severe, non-specific chest pain and purpura. Laboratory studies revealed thrombocytopenia 51¥103 (normal values 140-440¥103). Thrombotic thrombocytopenic purpura (TTP) with high titers of ADAMTS-13 antibody was diagnosed. TTP progression could not be halted despite treatment, necessitating administration of rituximab and removal of breast implants, what resulted in complete remission. Autoimmune/inflammatory syndrome induced by adjuvants (ASIA) was diagnosed retrospectively.2