Association of HLA-B*41 with Henoch-Schönlein Purpura in Spanish Individuals Irrespective of the HLA-DRB1 Status

Fernanda Genre¹, Raquel López-Mejías¹, Belén Sevilla Pérez², Santos Castañeda³, Norberto Ortego-Centeno², Javier Llorca⁴, Begoña Ubilla¹, Trinitario Pina Murcia¹, Vanesa Calvo-Río⁵, Ana Márquez⁶, Luis Sala-Icardo⁷, Jose A. Miranda-Filloy⁸, Marta Conde-Jaldón⁹, Lourdes Ortiz-Fernández⁹, Juan María Blanco-Madrigal¹⁰, Eva Galindez-Agirregoikoa¹⁰, Francisca González Escribano⁹, Javier Martin¹¹, Ricardo Blanco¹² and MA González-Gay¹, ¹Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain, ²Medicine Department, Hospital Universitario San Cecilio, Granada, Spain, ³Rheumatology, Hospital Universitario de La Princesa, IISP, Madrid, Spain, ⁴Department of Epidemiology and Computational Biology, School of Medicine, University of Cantabria, and CIBER Epidemiología y Salud Pública (CIBERESP), IDIVAL, Santander, Spain, ⁵Av. Cardenal Herrera Oria s/n - Lab. 201, Epidemiology, Genetics and Atherosclerosis Research Group on Systemic Inflammatory Diseases, Rheumatology Division, IDIVAL, Santander, Spain, ⁶Instituto de Parasitologia y Biomedicina López-Neyra (IPBLN-CSIC) and Systemic Autoimmune Diseases Unit, Hospital Clínico San Cecilio, Granada, Spain, ⁷Rheumatology, Hospital Universitario de La Princesa. IIS La Princesa, Madrid, Spain, ⁸Hospital Universitario Lucus Augusti, Rheumatology Division, Lugo, Spain, ⁹Immunology department, Hospital Universitario Virgen del Rocío, Sevilla, Spain, ¹⁰Rheumatology Department. Basurto University Hospital, Bilbao, Spain, ¹¹Immunology, Instituto de Parasitología y Biomedicina López-Neyra, IPBLN-CSIC, Armilla (Granada), Spain, ¹²Hospital Marques de Valdecilla, Santander, Spain

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Vasculitis

Session Information

Title: Vasculitis

Session Type: Abstract Submissions (ACR)

Background/Purpose: Henoch-Schönlein purpura (HSP), the most common type of primary small-sized blood vessel leukocytoclastic vasculitis, is characterized by infiltration of the small blood vessels with polymorphonuclear leukocytes and presence of leukocytoclasia. Skin, joint, gastrointestinal tract and kidney involvement may be affected in patients with HSP. Although the etiology of HSP remains unknown, environmental factors and a susceptible genetic background have been associated with HSP. In this regard, the role of the HLA (human leukocyte antigen) region in the HSP pathogenesis has previously been studied in small series of HSP patients, but contradictory results were obtained. To further establish whether HLA-B alleles are implicated in the susceptibility and severity of HSP, we performed a study that encompassed the largest series of HSP patients ever assessed for genetic studies in Caucasian individuals.

Methods: Our study population included 279 Spanish patients diagnosed with HSP and 335 sex and ethnically matched controls. HSP patients fulfilling the American College of Rheumatology (Arthritis Rheum 1990; 33: 1114-21) and the Michel et al (J Rheumatol 1992; 19: 721-8) classification criteria were recruited from Hospital Universitario Lucus Augusti (Lugo), Hospital Universitario Marqués de Valdecilla (Santander), Hospital Universitario La Princesa (Madrid), Hospital Universitario San Cecilio (Granada) and Hospital Universitario de Basurto (Bilbao). HLA-B phenotypes were determined using PCR-SSOP Luminex.

Results: HLA-B*41 was significantly increased in patients with HSP compared to controls (p=0.0001, OR=3.68 [95% CI: 1.75-8.27]) even after adjusting the results for multiple testing correction (p=0.0018). Since previous studies suggest a potential association between HLA-DRB1*01 and HSP susceptibility, we also evaluated the implication of HLA-B*41 independently of HLA-DRB1*01 status in HSP patients and healthy controls. For this purpose we excluded from the analysis patients and controls carrying HLA-DRB1*01 alleles. Interestingly, the association remained statistically significant (p=0.01, OR=2.93 [95% CI: 1.20-7.14]).

Conclusion:

Our study indicates that HLA-B*41 is associated with the susceptibility to HSP in Spanish individuals, irrespective of HLA-DRB1 status.

This study was supported by European Union FEDER funds and “Fondo de Investigaciones Sanitarias” (PI12/00193) (Spain). RLM is a recipient of a Sara Borrell postdoctoral fellowship from the Instituto de Salud Carlos III at the Spanish Ministry of Health (Spain) (CD12/00425). FG and BU are supported by funds from the RETICS Program (RIER) (RD12/0009/0013) (Spain).

Disclosure:

F. Genre,
None;

R. López-Mejías,
None;

B. Sevilla Pérez,
None;

S. Castañeda,
None;

N. Ortego-Centeno,
None;

J. Llorca,
None;

B. Ubilla,
None;

T. Pina Murcia,
None;

V. Calvo-Río,
None;

A. Márquez,
None;

L. Sala-Icardo,
None;

J. A. Miranda-Filloy,
None;

M. Conde-Jaldón,
None;

L. Ortiz-Fernández,
None;

J. María Blanco-Madrigal,
None;

E. Galindez-Agirregoikoa,
None;

F. González Escribano,
None;

J. Martin,
None;

R. Blanco,
None;

M. González-Gay,
None.

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