HLA-DRB1*16 / HLA-DQB1*0301 Haplotypes Confer Susceptibility to Parry Romberg Syndrome

Introduction: Parry Romberg syndrome is a complex clinical entity characterized by progressive hemifacial atrophy. The differential diagnosis includes generalized scleroderma, morphea and CREST syndrome. These skin and soft tissue disorders are associated with polymorphic alleles of the HLA system. Thus, scleroderma is associated with HLA DR*11, CREST syndrome with HLA-DR*03, HLA-DR*01, while morphea does not have a direct association at least in mestizo population. 

Objective: The purpose of this paper was to explore the potential association between Parry Romberg syndrome and alleles of the HLA system, in order to understand the physiopathogenic mechanism and the role of ethnicity in the development of the disease in mestizo individuals. We proposed an immunogenetic characterization of the disease, a research area not explored before globally in this patients. 

Material and Methods: We included 24 patients with Parry Romberg Syndrome from the Plastic and Reconstructive Surgery Department at Hospital General "Dr. Manuel Gea Gonzalez" in Mexico City. The diagnosis was based upon clinical examination, imaging and skin histopathology studies.  The haplotypes of HLA involving HLA loci A, B, DR, DQ antigens were typified in 24 patients (48 haplotypes)  and the frequencies were further established. The results were compared with frequencies from a group of 99 Mexican Mestizo patient controls without history of autoimmune or metabolic disease.  The differences in gene frequencies were analyzed using nonparametric statistics that included Chi square test and Fisher's exact test, besides determining OR (odds ratio) and confidence intervals of 95%.

Results: Patients with Parry Romberg syndrome showed a significant increase in HLA-DRB1*16 (g.f: 14% PRS vs 1% in normal p=0.002; OR: 6.5, 95% CI. (1.9 - 21.7) and diminished HLA-DR*07 (p=0.03; OR: 0.17, CI 95% 0.02 – 1.2). Furthermore, it was found that the HLA-DR*16 is part of the haplotypes: HLA-DRB1*16 / DQB1*0301, in combination with HLA-B*39, HLA-B*15 alleles and HLA-B*35, in contrast with normal population which showed the  HLA-DQB1*0502 allele

Discussion: Our research group has performed several HLA studies in the past, mainly in the organ transplantation and autoinmmune diseases scenarios. We have found that immunogenetic studies provide important data to understand the nature of diseases and establish medical and surgical treatment protocols. Data obtained from this study suggest that the haplotype HLA-DRB1*16 / HLA-DQB1*0301 confers susceptibility to Parry Romberg Syndrome. This haplotype has an indigenous origin, which suggests that mexican mestizo population with the syndrome, are influenced by the genetic background of the Native American. Also, since the risk alleles (HLA-DR*11, HLA-DR*01 and HLA-DR*03) for diseases traditionally related to the syndrome, were actually found diminished in this study, it suggests that Parry Romberg Syndrome is an entirely different entity, as proved by HLA studies.

Conclusion:the haplotype HLA-DRB1*16 / HLA-DQB1*0301 confers susceptibility to Parry Romberg Syndrome in mestizo population. To our best  knowledge, this is the first genetic study with this characteristics performed worldwide in patients with this syndrome.