Narjes Soleimanifar; Sara Assaadiasl; Mohammed Sameer Al-Shammari; Abdol-Rahman Rostamian; Maryam Sadr; Sepideh Shahkarami; Hanieh Mojtahedi; Mohammad Hossein Nicknam
Abstract
Background: Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of ...
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Background: Ankylosing spondylitis (AS) is a chronic autoimmune disorder characterized by the fusion of vertebral joints and axial arthritis. The programmed death-1 (PD-1) inhibitory receptor has a pivotal role in controlling T cell function and may have a significant impact on the pathogenesis of autoimmune diseases such as AS pathogenesis. Objective: To investigate PD-1 gene expression and its epigenetic regulation by detecting methylated CpG islands in the regulatory sites of the gene. This will provide insight into the mechanisms involved in the disease. Methods: 30 AS patients and 30 healthy individuals were examined to detect the 16 CpG islands in intron 1 using bisulfite conversion and methylation-specific PCR technique. In addition, RNA samples were isolated from fresh peripheral blood mononuclear cells (PBMCs), and after complementary DNA (cDNA) synthesis, the expression level of the PD-1 gene was evaluated using Real-Time PCR. Results: The CpG islands located in the intronic zone of the PD-1 gene were hyper-methylated in both the patients with AS and the healthy controls. The gene expression of PD-1 was significantly downregulated in AS patients compared with the controls (p=0.017). A negative correlation between the Bath Ankylosing Spondylitis Disease Activity Index and PD-1 gene expression was also revealed. Conclusion: The low level of PD-1 gene expression is implicated in the pathogenesis of AS. However, in both groups, the methylation level of the intron 1 CpG islands of the PD-1 gene suggests that other regulatory mechanisms are more relevant to PD-1 gene expression than methylation in the intron.
Jingjing Zhang; Shasha Zhang; Shuo Xu; Xiaoyun Zhang; Jiasong Li; Zhengzheng Ji; Qingyi Liu; Zhanjun Guo
Abstract
Immune Checkpoint Inhibitors (ICIs) have dramatically revolutionized the therapeutic approaches by which we treat a series of cancers accompanied by immune-related adverse events (irAEs). Herein, we reported an intrahepatic cholangiocarcinoma male patient with a history of ankylosing spondylitis developing ...
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Immune Checkpoint Inhibitors (ICIs) have dramatically revolutionized the therapeutic approaches by which we treat a series of cancers accompanied by immune-related adverse events (irAEs). Herein, we reported an intrahepatic cholangiocarcinoma male patient with a history of ankylosing spondylitis developing pulmonary arterial hypertension (PAH) under ICI combined therapy with pembrolizumab and lenvatinib. The indirect measurement of cardiac ultrasound showed a pulmonary artery pressure (PAP) of 72mmHg after 21 three-week cycles of ICI combined therapy. The patient partially responded to the treatment of glucocorticoid and mycophenolate mofetil. The PAP decreased to 55mmHg 3 months after the ICI combined therapy was discontinued, but increased to 90mmHg after the ICI combined therapy was rechallenged. We treated him with adalimumab -an antitumor necrosis factor-alpha (ani-TNF-α) antibody- combined with glucocorticoid and immunosuppressants under lenvatinib monotherapy. The patient responded again with PAP decreasing to 67mmHg after 2 two-week cycles of adalimumab. Accordingly, we diagnosed him to have irAE-related PAH. Our findings supported the use of glucocorticoid disease-modifying antirheumatic drugs (DMARDs) as a treatment option in refractory PAH.
Tahereh Mousavi; Hadi Poormoghim; Maziar Moradi; Nader Tajik; Farhad Shahsavar; Behnam Asadifar
Abstract
Background: The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs). Objective: We investigated the HLAC and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence ...
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Background: The HLA class I molecules serve as ligands for both T cell receptors and killer cell immunoglobulin-like receptors (KIRs). Objective: We investigated the HLAC and HLA-Bw4 alleles as well as KIRs expression on CD56 positive lymphocytes to evaluate whether these genes and molecules could influence Ankylosing spondylitis (AS) susceptibility, alone or in combination. Methods: We typed 40 AS patients and 40 normal controls for HLA-C asn80 (group 1) and HLA-C lys80 (group 2), HLA-B Bw4thero, HLA-B Bw4iso and HLA-A Bw4 alleles by PCR-SSP method. We also assessed the expression of KIR2DL1/2DS1, KIR2DL2/2DL3, KIR3DL1 and KIR2DS4 by flow cytometry. The Pearson chi-square or Fisher exact test was performed for statistical analysis. Results: The frequency of HLA-B Bw4iso but not HLA-B Bw4thero and HLA-A Bw4, ligand for the inhibitory KIR3DL1, was significantly reduced in AS patients as compared with controls (p<0.01). No significant differences were observed in gene carrier frequencies of HLA-C group 1 and 2 between AS and controls. Although no differences were found in the expression of KIR receptors between AS and normal subjects, we found that expression of KIR3DL1 in the presence of HLA Bw4-Biso gene was reduced in patients with AS compared to healthy controls (p<0.009). Conclusion: We conclude that HLA-B Bw4iso, the ligand of inhibitory KIR3DL1, with and without the expression of KIR3DL1 might be involved in protection against AS. Our results suggest that besides the HLA and KIR genotype, expression levels of KIRs may be involved in the pathogenesis of AS disease
Salomeh Fouladi; Minoo Adib; Mansoor Salehi; Hadi Karimzadeh; Zahra Bakhshiani; Vajiheh Ostadi
Abstract
Background: HLA-B*27 is strongly associated with ankylosing spondylitis (AS). It represents a family of alleles that differ among ethnic groups. Objective: The aim of this study was to determine the distribution of HLA-B*27 alleles in AS patients and healthy controls in Isfahan (Iran). Methods: Sixty ...
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Background: HLA-B*27 is strongly associated with ankylosing spondylitis (AS). It represents a family of alleles that differ among ethnic groups. Objective: The aim of this study was to determine the distribution of HLA-B*27 alleles in AS patients and healthy controls in Isfahan (Iran). Methods: Sixty AS patients and 430 healthy blood donors were selected. All subjects were HLA-B*27 positive by flow cytometry. HLAB* 27 subtypes were determined by PCR-SSP. Results: Forty patients (66.7%) and 17 controls (3.95%) were HLA-B*27 positive. Subtypes detected by PCR-SSP were B*2705, B*2702, B*2704 and B*2707. One patient was B*2702/B*2710. No significant difference was found in the distribution of these alleles between AS patients and controls. Conclusion: Although Caucasian subtypes are predominant among Iranians, this population is characterized by a combination of both specific Caucasian and Oriental subtypes. However such results should be interpreted carefully because of the small sample size in our investigation and definitive conclusion awaits more ethnicgroup studies.
