ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1975

Behcet’s Disease Lies in the “B” Holder. New Associations in Disease Susceptibility and Manifestations

Mohanad Elfishawi1,2, Sally Elfishawi3, Ghada Mossallam3, Paul Norman4, Jill Hollenbach5, Maneesh Misra5, Gonzalo Montero Martin6, Helma de Bruin7, Leos Van de Pasch7, Erik Rozemuller7, Marcelo Fernandiz-Vina6, Adriana Abrudescu8 and Khaled Zaky9, 1Internal Medicine, Icahn School of Medicine at Mount Sinai, Queens Hospital Center, New York, NY, 2Rheumatology, Kasr Alainy Hospital, Cairo University, Cairo, Egypt, 3Clinical pathology and Immunology laboatory, National Cancer Institute, Cairo University, Cairo, Egypt, 4Division of Personalized Medicine and Department of Immunology, University of Colorado School of Medicine, Denver, CO, 5Department of Neurology, University of California San Francisco, San Francisco, CA, 6Department of Pathology, Stanford University,School of medicine, Palo Alto, CA, 7GenDx, Utrecht, Netherlands, 8Internal Medicine and Rheumatology, Icahn School of Medicine at Mount Sinai, Queens Hospital center, NYC, NY, 9Rheumatology and Rehabilitation, Faculty of medicine, Al-Azhar University, Cairo, Egypt

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: , , ,

Session Information

Date: Tuesday, October 23, 2018

Session Title: Genetics, Genomics and Proteomics Poster

Session Type: ACR Poster Session C

Session Time: 9:00AM-11:00AM

Background/Purpose:

Behçet’s disease is a multisystem disease affecting young adults with variable vessel vasculitis as its underlying pathology. Previous studies in Behçet’s disease linked it to the Human Leucocytic antigens (HLA) class I molecules however the use of High-resolution Next Generation Sequencing (NGS) wasn’t adopted before for all HLA loci (both class I and II ) analysis along with the haplotype analysis. This study aims to identify the Behcet disease susceptibility with class I and II HLA alleles using NGS along with their haplotype analysis to help better understand the disease process and to find a possible association with disease manifestations and severity.

Methods:

Sixty patients from specified geographical distribution diagnosed according to the International Study Group (ISG) criteria for Behçet’s disease along with 160 normal geographically ethnic-matched controls were typed for the class I HLA alleles and from the control group, 40 control samples were typed for class II HLA alleles.

The work was a part of participation in the 17th International Histocompatibility and Immunogenetics Workshop (IHIWS) in the disease association component during which HLA was typed for patients and 40 control subjects at the allelic level by NGS high resolution typing for 11 loci (HLA-A, B, C, DRB1, DRB3/4/5, DQA1, DQB1, DPA1, DPB1). The control group was then expanded for an additional 120 control subjects typed for HLA class I loci (A, B and C) along with data analysis and haplotype analysis for the results.

Results:

Sixty patients were enrolled with mean age 35.28 (±9.82 years) with 54 males (90%). The main clinical manifestations were oral ulcers (100%), genital ulcers (100%), eye involvement (55%) neurological involvement (28%) and vascular involvement (35%). Furthermore, (33%) had bilateral visual acuity < or = 6/60 fulfilling the diagnosis of legal blindness

HLA class I alleles A*68:02:01,B*51:08:01,C*16:02:01 showed highest level of association with Behcet disease patients with an OR =3 (p=0.01) and OR=18.6 (p<0.0000001) and OR=6.7 (p<0.000001) respectively. As for HLA class I haplotypes HLA class I B*51:08, C*16:02 haplotype was highly associated with susceptibility (OR=17.7, p<0.000001). HLA class I B*51 and A*68 were significantly associated with legal blindness (OR=10.1, p<0.005) and (OR=8.1, p=0.023)

Conclusion:

Among the studied Behçet’s Patients, HLA-B*51:08:01 is the most frequent susceptibility allele in contrast to other reported populations. Risk of Severe ocular involvement progressing to the blindness of patients was more than 10 folds increased in HLA-B51 positive patients as compared to other patients. HLA-B51 together with HLA-A68 both hold the increased risk of blindness and permanent morbidity in patients with Behcet disease, which if known at diagnosis would modify treatment options in order to salvage the patients’ eyesight. Higher resolution analysis of HLA class I alleles and haplotypes specially HLA-B is valuable in knowing susceptibility and aiding in disease control and decreasing ocular morbidity in Behcet disease patients

Disclosure: M. Elfishawi, None; S. Elfishawi, None; G. Mossallam, None; P. Norman, None; J. Hollenbach, None; M. Misra, None; G. M. Martin, None; H. de Bruin, GenDX, 3; L. Van de Pasch, GenDx, 3; E. Rozemuller, Gendx, 1, 3; M. Fernandiz-Vina, None; A. Abrudescu, None; K. Zaky, None.

To cite this abstract in AMA style:

Elfishawi M, Elfishawi S, Mossallam G, Norman P, Hollenbach J, Misra M, Martin GM, de Bruin H, Van de Pasch L, Rozemuller E, Fernandiz-Vina M, Abrudescu A, Zaky K. Behcet’s Disease Lies in the “B” Holder. New Associations in Disease Susceptibility and Manifestations [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 10). https://acrabstracts.org/abstract/behcets-disease-lies-in-the-b-holder-new-associations-in-disease-susceptibility-and-manifestations/. Accessed January 17, 2020.

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