HLA Class II Polymorphisms and Susceptibility to Recurrent Respiratory Papillomatosis

Abstract

Recurrent respiratory papillomatosis (RRP) is characterised by multiple laryngeal papillomas. Left untreated, the lesions enlarge, spread, and endanger the airway. Medical treatments are unsatisfactory, and repeated surgery remains the mainstay of therapy. RRP is caused by human papillomavirus (HPV) infection. However, since oral HPV infection is common and RRP is rare, other host and/or viral factors may contribute to pathogenesis. In an attempt to identify such factors, we have investigated 60 patients. The patients were HLA class I, II, and tumor necrosis factor TNF typed by sequence-specific primer PCR, and the results compared to those for 554 healthy controls by using Fisher's exact test. Peripheral blood mononuclear cell proliferative responses of 25 controls and 10 patients to HPV-11 L1 virus-like particles (VLP) were compared. Short-term VLP-specific T-cell lines were established, and recognition of L1 was analyzed. Finally, the L1 open reading frames of HPV isolates from four patients were sequenced. Susceptibility to RRP was associated with HLA DRB1*0301 (33 of 60 patients versus 136 of 554 controls, P < 0.0001). The three most severely affected patients were homozygous for this allele. A range of T-cell proliferative responses to HPV-11 VLP were observed in DRB1*0301-positive healthy donors which were comparable to those in DRB1*0301-negative controls. Individuals with juvenile-onset RRP also mounted a range of VLP responses, and their magnitude was negatively correlated with the clinical staging score (P = 0.012 by the Spearman rank correlation). DRB1*0301-positive patients who responded to L1 recognized the same epitope as did matched controls and produced similar cytokines. Sequencing of clinical isolates excluded the possibility that nonresponsiveness was the result of mutation(s) in L1.

Detection of Anti-HPV11-L1 Antibodies in Immune Sera from Patients Suffering from Recurrent Respiratory Papillomatosis Using ELISA

“…Therefore such precise quantitative comparison was not possible in our study. The overall HPV genotype prevalence in our study group was consistent with data published earlier, demonstrating that HPV6 and HPV11 are the dominant types in JORRP patients (12,16,20); however, in our study more cases of HPV11-related papillomas were observed (70%), whereas it was previously reported that the predominant genotype in JORRP patients was HPV6 (19). This may be due to the particular HPV epidemiology seen in our Polish population.…”

“…It has also been proposed that genes coding for HLA II may play a role in JORRP development. Different HLA II alleles were identified, and a worse RRP course was seen in homozygotes bearing ''defective'' alleles (12).…”

HLA Loci and Respiratory Infectious Diseases

“…This same study found preliminary evidences for an HLA-DRB1*14 association in juvenileonset disease and a HLA-B*27 association in adult-onset disease [135] . Another study confirmed the association between HLA-DRB1*03: 01 and the severity of the disease in Caucasian patients and found also a positive association with DRB1*01: 02, DQB1*02: 01 and DQB1*02: 02 and a protective effect for DQB1*06: 02 [136] .…”

Papilomatosis respiratoria recurrente en paciente pediátrico: reporte de un caso

“…However, it is still unclear whether HPV causes this alteration in immunity or if children with impaired immunity develop RRP. As well as the susceptibility to cervical cancer caused by HPV has been related to some specific HLA alleles, similarly it has been seen that this association is fulfilled in patients with RRP, where certain alleles influence the course of the disease, favoring the severity [8][9][10] or, on the contrary, fulfilling a protective role 11,12 .…”

“…HLA-DRB1*14 has been associated with susceptibility to JO-RRP, whereas HLA-DRB1*0301 with susceptibility to AO-RRP. Interestingly, patients homozygous for HLA-DRB1*0301 show a more severe clinical picture 8 . Also, it has been shown that the HLA-DQA and HLA-DQB1 alleles present in different proportions in children with RRP regarding their controls.…”