The role of key biomarkers in lymphatic malformation: An updated review.

The lymphatic system, crucial for tissue fluid balance and immune surveillance, can be severely impacted by disorders that hinder its activities. Lymphatic malformations (LMs) are caused by fluid accumulation in tissues owing to defects in lymphatic channel formation, the obstruction of lymphatic vessels or injury to lymphatic tissues. Somatic mutations, varying in symptoms based on lesions' location and size, provide insights into their molecular pathogenesis by identifying LMs' genetic causes. In this review, we collected the most recent findings about the role of genetic and inflammatory biomarkers in LMs that control the formation of these malformations. A thorough evaluation of the literature from 2000 to the present was conducted using the PubMed and Google Scholar databases. Although it is obvious that the vascular endothelial growth factor receptor 3 mutation accounts for a significant proportion of LM patients, several mutations in other genes thought to be linked to LM have also been discovered. Also, inflammatory mediators like interleukin-6, interleukin-8, tumor necrosis factor-alpha and mammalian target of rapamycin are the most commonly associated biomarkers with LM. Understanding the mutations and genes expression responsible for the abnormalities in lymphatic endothelial cells could lead to novel therapeutic strategies based on molecular pathways.

Key biomarkers in cerebral arteriovenous malformations: Updated review.

The formation of vascular networks consisting of arteries, capillaries, and veins is vital in embryogenesis. It is also crucial in adulthood for the formation of a functional vasculature. Cerebral arteriovenous malformations (CAVMs) are linked with a remarkable risk of intracerebral hemorrhage because arterial blood is directly shunted into the veins before the arterial blood pressure is dissipated. The underlying mechanisms responsible for arteriovenous malformation (AVM) growth, progression, and rupture are not fully known, yet the critical role of inflammation in AVM pathogenesis has been noted. The proinflammatory cytokines are upregulated in CAVM, which stimulates overexpression of cell adhesion molecules in endothelial cells (ECs), leading to improved leukocyte recruitment. It is well-known that metalloproteinase-9 secretion by leukocytes disrupts CAVM walls resulting in rupture. Moreover, inflammation alters the angioarchitecture of CAVMs by upregulating angiogenic factors impacting the apoptosis, migration, and proliferation of ECs. A better understanding of the molecular signature of CAVM might allow us to identify biomarkers predicting this complication, acting as a goal for further investigations that may be potentially targeted in gene therapy. The present review is focused on the numerous studies conducted on the molecular signature of CAVM and the associated hemorrhage. The association of numerous molecular signatures with a higher risk of CAVM rupture is shown through inducing proinflammatory mediators, as well as growth factors signaling, Ras-mitogen-activated protein kinase-extracellular signal-regulated kinase, and NOTCH pathways, which are accompanied by cellular level inflammation and endothelial alterations resulting in vascular wall instability. According to the studies, it is assumed that matrix metalloproteinase, interleukin-6, and vascular endothelial growth factor are the biomarkers most associated with CAVM and the rate of hemorrhage, as well as diagnostic methods, with respect to enhancing the patient-specific risk estimation and improving treatment choices.

A comprehensive review of the epidemiology and clinical features of 91 cases with Buerger's disease.

BACKGROUND: Thromboangiitis Obliterans (TAO) is a disease of small and medium-sized arteries with an unclear natural course. This study aims to establish a national registry of the disease to gain a better understanding of its epidemiology and clinical course. METHOD: This study was a cohort study of 242 patients with a high probability of TAO admitted to Mashhad University of Medical Sciences (MUMS) hospitals from 2000 to 2015. Of these, 91 patients with a confirmed diagnosis were included in the study (90 males and 1 female) with a mean age of 35 ± 7.8 years. RESULTS: The most common symptom upon onset of the disease was paresthesia (29.7%), followed by cold sensitivity and paresthesia (93.4%) during the progression of the disease and Raynaud syndrome or vasospasm (93.9%) in the active phase. The right lower limb was the most commonly affected limb (46.2%), and presenting ischemic symptoms in 48.4%.Statistics indicated a positive correlation between the duration of Burger's disease and the number of affected limbs (p = 0.001). There was no effect of disease duration on the likelihood of amputations (p = 0.28). CONCLUSION: Some patients may experience mild, subtle symptoms for years before the initial signs and symptoms appear, which can be severe and rapidly progress to the point of requiring amputation.We suggest that the diagnostic criteria for Buerger's disease should be revised in light of the presence of atherosclerosis and its associated risk factors, which present a challenge in terms of diagnosis and treatment. Clinical experience will be of great importance in this regard.

Different types of cell death in vascular diseases.

In a mature organism, tissue homeostasis is regulated by cell division and cell demise as the two major physiological procedures. There is increasing evidence that deregulation of these processes is important in the pathogenicity of main diseases, including myocardial infarction, stroke, atherosclerosis, and inflammatory diseases. Therefore, there are ongoing efforts to discover modulating factors of the cell cycle and cell demise planners aiming at shaping innovative therapeutically modalities to the therapy of such diseases. Although the life of a cell is terminated by several modes of action, a few cell deaths exist-some of which resemble apoptosis and/or necrosis, and most of them are different from one another-that contribute to a wide range of functions to either support or disrupt the homoeostasis. Even in normal physiological conditions, cell life is severe within the cardiovascular system. Cells are persistently undergoing stretch, contraction, injurious metabolic byproducts, and hemodynamic forces, and a few of cells sustain decade-long lifetimes. The duration of vascular disease causes further exposure of vascular cells to a novel range of offences, most of which induce cell death. There is growing evidence on consequences of direct damage to a cell, as well as on responses of adjacent and infiltrating cells, which also have an effect on the pathology. In this study, by focusing on different pathways of cell death in different vascular diseases, an attempt is made to open a new perspective on the therapeutic goals associated with cell death in these diseases.

Humoral and cellular immune response to Buerger's disease.

OBJECTIVE: Thromboangiitis obliterans is a nonatherosclerotic occlusive disease, affecting small to moderate sized arteries of the upper and lower extremities, leading to progressive inflammation and clot formation. However, the role of humoral and cell-mediated immunity in the development of this disease has not been clearly identified. The present study was intended to investigate the humoral and cellular immune response in patients with Buerger's disease with different disease severity. METHODS: In an observational study, 80 male patients with Buerger's disease were included and categorized into three groups (mild, moderate, and severe) based on clinical manifestations. After blood sampling, cellular phenotypes were determined, and erythrocyte sedimentation rate, immunoglobulins (Ig) A, M, G, and E, as well as C3 and C4 components of the complement system and complement hemolytic activity (CH50) were measured. RESULTS: The mean age of the patient was 42.85 ± 8.39 years. Pulse abnormality, cold intolerance, and claudication were the most common symptoms. Eleven (13.75%), 46 (57.50%), and 23 (28.75%) patients had mild, moderate, and severe symptoms. Regression analyses showed that the presence of severe symptoms was significantly associated with elevated erythrocyte sedimentation rate and C4 levels (p < 0.05). CONCLUSION: Buerger's disease in severe cases was associated with increased erythrocyte sedimentation rate and abnormal C4 levels. The alterations in these inflammatory biomarkers might be due to a secondary inflammatory response to the presence of ulcer or gangrene and the inflammatory process in patients with severe symptoms.

Digital pressure and oxygen saturation measurements in the diagnosis of chronic hemodialysis access-induced distal ischemia.

OBJECTIVE: Hemodialysis access-induced distal ischemia (HAIDI) can be classified as acute (on the first postoperative day), subacute (≤1 month), or chronic (>1 month), based on the time of onset after access creation. The diagnosis is mainly clinical. However, performing additional tests is beneficial in further assessment of patients. The purpose of this study was to evaluate the use of finger pressure and oxygen saturation measurements for the diagnosis of chronic HAIDI. METHODS: A total of 20 patients with chronic HAIDI (cases) and 40 asymptomatic hemodialysis patients (controls) were matched for age, sex, etiology of end-stage renal disease, and type of arteriovenous access. Basal digital pressure (BDP), digital pressure during manual compression of access, digital brachial index (DBI), change in digital pressure with access compression (CDP), digital pressure of the contralateral side, and bilateral oxygen saturation (O2 Sat) were measured in all patients. RESULTS: In the case group, compression of the arteriovenous fistula (AVF) increased mean BDP from 61 ± 26 to 118 ± 28 mm Hg (P < .001), which failed to reach the non-AVF side mean digital pressure of 151 ± 25 mm Hg (P < .001). In addition, O2 Sat of the AVF side was significantly lower than the contralateral side (92.9% ± 2.1% vs 95.6% ± 1.4%; P = .001). Among the controls, manual AVF compression raised the mean BDP from 114 ± 36 mm Hg to 133 ± 29 mm Hg (P < .001), which was still significantly lower than the contralateral side mean digital pressure of 141 ± 30 mm Hg (P = .002). In addition, O2 Sat values of the two sides were different (96.7% ± 2.1% vs 97.1% ± 1.9%; P = .01). Comparing the cases and controls, the mean BDP (61 ± 26 mm Hg vs 114 ± 36 mm Hg; P < .001), DBI (0.44 ± 0.16 vs 0.82 ± 0.19; P < .001), and O2 Sat (92.9% ± 2.1% vs 96.7% ± 2.1%; P < .001) were significantly lower and CDP (57 ± 24 mm Hg vs 19 ± 17 mm Hg; P < .001) was significantly higher in the cases than in the controls. The optimal discriminatory thresholds of 80 mm Hg for BDP, 0.7 for DBI, 40 mm Hg for CDP, and 94% for O2 Sat were determined. CONCLUSIONS: Digital pressure and O2 Sat measurements are useful additional methods to assist in the clinical evaluation of hemodialysis patients with access-related hand ischemia. BDP <80 mm Hg, DBI <0.7, CDP >40 mm Hg, and O2 Sat <94% are associated with chronic HAIDI.

Buerger's disease in the northeast of Iran: Epidemiology and clinical features.

BACKGROUND: The aim of this study is to present our long-term clinical experience in describing a clinical picture of Buerger's disease in our region. MATERIALS AND METHODS: In a retrospective study, files of 225 patients who were admitted to the hospital with diagnosis of thromboangiitis obliterans in a 10 year period from 2000 to 2010 were reviewed. All data including demographic, signs and symptoms, history of previous illness, history of smoking, medications, laboratory tests, angiography, and details of surgical operation were obtained. RESULTS: A total of 222 (98.7%) and 3 (1.3%) of patients were male and female, respectively. Average age of hospitalized patients was 40.7 ± 8.5 (20-62) years. A total of 200 patients (88.9%) were active cigarette smokers while 168 (74.7%) of them were opium addicts. The most prevalent symptoms were chronic ulcers (80%) and claudication (63.6%). Minor and major amputation was required in 113 (50.2%) and 41 (18.4%) patients, respectively. Amputation was carried out on the lower limb (80%), upper limb (4.1%), or on both (15.1%). Also, four patients underwent revascularization through surgical bypass procedures. CONCLUSIONS: The diagnosis and treatment of Buerger's Disease is still a challenge in those communities where the disease is endemic. Therefore, identifying the natural course of the disease can play a pivotal role in the diagnosis and treatment of these patients.

Effect of static magnetic field therapy on diabetic neuropathy and quality of life: a double-blind, randomized trial.

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM) that can cause annoying symptoms. To address this condition, several treatment approaches have been proposed, including static magnetic field (SMF) therapy, which has shown promise in treating neurological conditions. Therefore, this study aimed to investigate the effects of SMF therapy on symptomatic DPN and the quality of life (QoL) in patients with type 2 diabetes. METHODS: A double-blind, randomized, placebo-controlled trial was conducted from April to October 2021. Sixty-four DPN patients (20 males, 44 females) were recruited for the study via invitation. The participants were divided into two groups: the magnet group, which used magnetic ankle bracelets (155 mT) for 12 weeks, and the sham group, which used non-magnetic ankle bracelets for the same duration. Neuropathy Symptom Score (NSS), Neuropathic Disability Score (NDS), and Visual Analogue Scale (VAS) were used to assess neuropathy symptoms and pain. In addition, the Neuropathy Specific Quality of Life Questionnaire (Neuro-QoL) tool was used to measure the patients' quality of life. RESULTS: Before treatment, there were no significant differences between the magnet and sham groups in terms of the NSS scores (P = 0.50), NDS scores (P = 0.74), VAS scores (P = 0.17), and Neuro-QoL scores (P = 0.82). However, after 12 weeks of treatment, the SMF exposure group showed a significant reduction in NSS scores (P < 0.001), NDS scores (P < 0.001), VAS scores (P < 0.001), and Neuro-QoL scores (P < 0.001) compared to the baseline. The changes in the sham group, on the other hand, were not significant. CONCLUSION: According to obtained data, SMF therapy is recommended as an easy-to-use and drug-free method for reducing DPN symptoms and improving QoL in diabetic type-2 patients. Trial registration Registered at Iranian Registry of Clinical Trials: IRCT20210315050706N1, 2021/03/16.

Assessment of Neutrophil Extracellular Traps (NETs) and Macrophage Ratio in the Inner and Outer Area of Carotid Artery Stenosis.

Background & Objective: It is noteworthy that majority of the data links neutrophil extracellular traps (NETs) to human arterial thrombosis. In the current study, extracellular neutrophil networks and macrophage polarization were assessed in the area outside and inside the Carotid artery stenosis. Methods: The sample of Carotid plaque of the patient was divided into two halves with a transverse incision; the terms inner part and outer part were used for the plaque's inner part and the adjacent area. Samples were sorted in 10% formalin for CD163, CD11c, MPO, and histone H3 immunohistochemical assessment, while part of the sample was stored at -80°C for western blotting assay for PDA4 marker. Results: Results of this study showed that the extracellular neutrophil in the inner part of the Carotid plaque was significantly increased (P<0.0001), while the number of M1 and M2 macrophages was higher in the inner part compared with the outer part of the Carotid plaque (P<0.0001). Conclusion: The distribution of NETs and the ratio of macrophages may be different in the inner and outer aspects of arterial plaque.

Presentation of hospital outcomes and different treatment methods of patients with budd-Chiari syndrome: a report from two tertiary hospitals in iran.

OBJECTIVE: The aim of this study was to report common presentations of Budd-Chiari syndrome (BCS) and the early outcome of different treatment methods in two tertiary hospitals in Iran. SUBJECTS AND METHODS: This case series study was performed on 21 patients (mean age: 42 ± 13.09 years; 11 male, 52.4%, and 10 female, 47.6%) admitted for treatment of BCS in two tertiary referral centers in Mashhad, Iran, between 2002 and 2008. All required data of signs, underlying etiology, treatment methods and in-hospital mortality were gathered from patients' medical records. RESULTS: Angiographic and sonographic findings showed that the most frequent isolated location of obstruction was the inferior vena cava (n = 12, 57.1%). No distinct underlying disease was found in 6 (28.6%) patients. Eleven (52.4%) patients had web obstruction and 4 patients had other related underlying diseases. Treatment modalities consisted of medical follow-up in 12 (57.1%), angioplasty in 6 (28.6%), and surgery in 3 (14.3%) patients. Medical follow-up of 3 patients, 1 with angioplasty and 2 who had undergone surgery, disclosed that they had died before discharge from hospital. CONCLUSION: Higher age at diagnosis may reflect late diagnosis at an advanced stage of disease. We suggest that the early symptoms of this disease should be taken into account more seriously in differential diagnosis. Balloon angioplasty seems to be a more efficient method for treatment of BCS.

Para-Clinical and Immunological Evaluation in Buerger's Disease as a Suspected Autoimmune Disease: Case Series.

BACKGROUND: Autoimmunity causes the loss of normal immune homeostasis and involves the presence of autoantibodies and inflammation. Thromboangiitis obliterans or Buerger's disease (BD) refers to a type of vascular obstructive syndrome, with tobacco exposure accounting for disease formation and progression. However, the current understanding of autoimmunity is unclear in the context of BD, and the scientific findings are not enough to support autoimmune mechanisms. This study was aimed at investigating autoimmunity factors in patients with BD. METHODS: Clinical and experimental examinations were performed on 80 patients with BD. The diagnostic work-up for autoimmunity was composed of IgM rheumatoid factor (RF), anti-nuclear antibodies (ANA), The erythrocyte sedimentation rate (ESR), anti-cyclic citrullinated peptide (CCP) antibodies, Antiphospholipid antibodies (APA), Anti-cardiolipin antibodies (ACLA), anti-double-stranded DNA (ds-DNA), and extractable nuclear antigen (ENA) profile. Immunomarkers were detected using the quantitative enzyme-linked immunosorbent assay (ELISA). RESULTS: Raynaud's phenomenon (84.93%), cold sensitivity (76.25%), and claudication (73.75%) were the most common symptoms in the BD patients. Also, 64.29% represented with high ANA levels and positive RF, while 42.11% were found with increased ANA and ESR levels. The ANA/RF positive BD patients had ESR> 15 mm/hr and a high prevalence of cold sensitivity, claudication, and Raynaud's phenomenon (p> 0.05). CONCLUSION: There is a possibility of a non-specific autoimmune disposition among BD patients. RF and ANA could be considered for predicting disease progression.

Differences in autoimmunity factors based on the activity of thromboangiitis obliterans.

OBJECTIVE: The treatment of Buerger's disease (BD) presents a medical problem as its etiology is still unclear. In this study, our objective was to evaluate the serum levels of autoimmune markers in patients with different clinical features of BD. METHODS: In this study, 80 BD patients were categorized in three groups using a cross-sectional design: migratory thrombophlebitis, cold sensitivity, and skin discoloration (mild symptoms); chronic ulcers, claudication, and burning pain of the feet at night (moderate symptoms); pain at rest and spontaneous gangrene (severe symptoms). Enzyme-linked immunosorbent assay was performed to measure antibodies against immunoglobulin M rheumatoid factor (IgM RF), anti-nuclear antibodies (ANA), antibodies against cyclic citrullinated peptide (anti-CCP), antiphospholipid antibodies (APA), anti-cardiolipin antibodies (ACLA), anti-double stranded DNA (anti-dsDNA), and extractable nuclear antigen (ENA) profile. RESULTS: Patients with severe symptoms showed the lowest age (p=0.031), ESR (p<0.001), and highest prevalence of ischemia (p<0.001). In all the patients, the serum levels of ANA and IgM RF were higher than 1 U and 15 IU/mL, respectively. However, the progression of the disease from mild to moderate did not affect these markers significantly (p>0.05). Other markers were negative in patients with BD. CONCLUSION: The findings of this study indicate that BD may closely be correlated to transient autoimmune phenomena, despite the fact that further research is required to investigate how transient unspecific autoimmune reactions contribute to the BD pathogenesis.

Cytokine Analysis in Patients with Different Stages of Thromboangiitis Obliterans.

BACKGROUND: Studies suggest that cytokines are involved in the development of both inflammatory disorders and vascular diseases. OBJECTIVE: The changes in transforming growth factor ß (TGFß), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and interferon γ (IFNγ) with the progression of the thromboangiitis obliterans (TAO) symptoms were investigated in this research. METHODS: This study included 80 patients with TAO, who were selected from the Vascular and Endovascular Research Center in Alavi Hospital, from the year 2012 to 2016. They were then categorized into three groups: Mild (migratory thrombophlebitis, cold sensitivity or Raynaud's phenomenon, and skin discoloration), moderate (chronic ulcers, claudication, and burning pain of the feet at night), and severe (pain at rest and spontaneous gangrene) symptoms. The serum levels of TGFß, IL6, TNFα, and IFNγwere determined by the ELISA method and compared among the groups. RESULTS: The first three predominant symptoms were pulse disorder (n = 76, 95.00%), cold intolerance (n = 61, 76.25%), and claudication (n = 59, 73.75%). A comparison of the analysis of covariance (ANCOVA) revealed that both TGFß and IL6 were dysregulated as the severity of the symptoms increased from the moderate to the severe stages; however, such changes were not significant (p > 0.05). In the multiple logistic regression model, increased TNFα levels were seen in the presence of moderate symptoms as compared to the severe ones (p < 0.05). CONCLUSION: It could be concluded that TNFα, as part of the defining cytokineproduction profile of T helper cells, can be significantly involved in the progression of TAO from the moderate to the severe stages.

The effect of platelet-rich plasma-fibrin glue dressing in combination with oral vitamin E and C for treatment of non-healing diabetic foot ulcers: a randomized, double-blind, parallel-group, clinical trial.

OBJECTIVE: The current study assesses the effects of platelet-rich plasma-fibrin glue (PRP-FG) dressing along with oral vitamin E and C on wound healing and biochemical markers in patients with non-healing diabetic foot ulcers (non-healing DFU). METHODS: This randomized controlled trial was performed on 25 patients with non-healing DFU. Patients were treated with PRP-FG dressing plus oral vitamin E and C (intervention group) or PRP-FG dressing plus placebo (control group) for 8 weeks. RESULTS: Eight weeks after treatment, six wounds in the intervention group and two wounds in the control group were completely closed, and also wound size significantly reduced in both intervention and control groups (p < 0.05). This reduction in wound size was significantly greater in the intervention group compared to the control group (p = 0.019). Also, a significant decrease in prooxidant-antioxidant balance (PAB) , ESR, and hs-CRP was observed in the intervention group compared to the control group (p < 0.05). CONCLUSION: Our results showed that PRP-FG dressing along with oral vitamin E and C could be used to increase wound healing in patients with non-healing DFU by enhancing the wound healing process and reducing oxidative stress. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov (CT.gov identifier: NCT04315909).

Brachio-basilic upper arm transposition fistulas vs. prosthetic brachio-axillary vascular access grafts-Which one is preferred for hemodialysis?

INTRODUCTION: There is still controversy on the use of brachio-basilic upper arm transposition fistula (BBAVF) and prosthetic brachio-axillary vascular access grafts (BAPTFE) in patients with no suitable cephalic veins for creating an autogenous brachio-cephalic fistula. METHODS: In a randomized controlled clinical trial, 60 hemodialysis patients who were not a suitable candidate for BCAVF were randomly assigned into two groups: BBAVF and BAPTFE. The patients were clinically followed up to 1 year and the patency rate and access-related complications were compared between the two groups. FINDINGS: Access failure rate in the BBAVF and BAPTFE groups was 30.0% and 36.6%, respectively. The primary patency time was 232.73 ± 113.36 and 261.53 ± 147.37 days, respectively (P = 0.40). Thrombosis formation and infection were the two main causes for access failure, yet indicating no significant difference between the two groups (P > 0.05). DISCUSSION: BBAVF and BAPTFE have comparable clinical outcomes in short-term follow-up. Therefore, BAPTFE can be used as an alternative vascular access for hemodialysis in patients who are not a suitable candidate for BBAVF.

Molecular mechanisms regulating immune responses in thromboangiitis obliterans: A comprehensive review.

Thromboangiitis obliterans (TAO) is a thrombotic-occlusive as well as an inflammatory peripheral vascular disease with unknown etiology. Recent evidence has supported the immunopathogenesis of the disease, however, the factors contributing to the altered immune function and vascular tissue inflammation are still unclear. This review was intended to collate the more current knowledge on the regulatory molecules involved in TAO from an immunoreactive perspective. The homeostasis of the immune system as well as a variety of progenitor cell populations appear to be affected during TAO and these alterations are associated with intrinsic signaling defects that are directing to an improved understanding of the crosstalk between angiogenesis and the immune system, as well as the potential of new co-targeting strategies applying both immunotherapy and angiogenic therapy.

The Association of HLA-A, B and DRB1 with Buerger's Disease.

BACKGROUND: Thromboangiitis obliterans (TAO), also known as Burger's disease, is a devastating disease affecting the arteries and veins of the upper and lower distal limbs most commonly afflicting young male smokers of low socioeconomic status. The expression of human leukocyte antigen (HLA)-A, B and -DRB1 genes have been implicated in the pathogenesis of TAO. Our study aimed to examine the association of different HLA-A, B and -DRB1 genes in TAO patients in the Iranian population. METHODS: A case-control study examining 55 Iranian patients with TAO and 500 healthy subjects was performed in Imam Reza hospital, Mashhad, Iran. The prevalence of major histocompatibility complex (MHC) class I (-A, -B) and class II (-DRB) alleles were determined for each participant. RESULTS: Our results revealed the HLA-A*03 (odds ratio [OR]=5.394), HLA-A*24 (OR=5.143), HLA-A*31 (OR=4.251), HLA-A*11 (OR=3.034), HLA-B*27 (OR=6.680), HLA-B*15 (OR=3.959), HLA-B*07 (OR=3.698), HLA-B*51 (OR=3.370), HLA-B*44 (OR=3.326), HLA-DRB1*16 (OR=20.583), HLADRB1* 04 (OR=8.960), HLA-DRB1*14 (OR=3.746), HLA-DRB1*03 (OR=2.303), and HLA-DRB1*15 (OR=2.111) alleles to occur at a significantly higher frequency in TAO patients compared to controls (p<0.05). The HLA-A*25, HLA-A*66, HLA-DRB1*08, HLA-DRB1*10, and HLA-DRB1*12 alleles resulted in infinite OR, and was associated with an increased risk of TAO. However, the alleles HLA-A*30, HLA-B*08, HLA-B*45, HLA-B*46, and HLA-B*53 were associated with a protective role against TAO with an OR = 0. CONCLUSION: This is the first study examining the HLA pattern in patients with Burger's disease in the Iranian population. Our findings have revealed an association between HLA class I and II alleles with TAO.