Background/Purpose: Chronic nonbacterial osteomyelitis (CNO) is an auto-inflammatory condition primarily affecting children with an estimated prevalence of 1 per 10⁵ – 10⁶.  It is characterized by relapsing episodes of localised bone inflammation.  Extraosseous manifestations, including psoriasis, Crohn’s disease and enthesitis-related arthritis, frequently occur in patients and relatives. However, no increased frequency of HLA class I alleles associated with these diseases, such as HLA-B*27 and HLA-C*06, has been shown in patients with CNO.  The aim of this study was to determine the frequency of HLA class I alleles in and Irish cohort of patients with CNO compared to Irish population frequencies.

Methods: 43 Irish children and adolescents currently attending paediatric rheumatology services with CNO were recruited.  Whole exome sequencing was performed on blood using Agilent SureSelect XT Human All Exon V6 kits and Illumina HiSeq 3000 with 150bp paired-end reads.  Reads were aligned to the hg19 reference genome using BWA software, duplicates removed using Picard tools and GATK software used to realign indels and call variants.  HLA alleles were predicted from whole exome sequencing results using Optitype software through the Nextflow nf-core/hlatyping pipeline (version 1.1.5). Comparison was made with previously published Irish HLA allele frequencies. Statistical analysis was performed in RStudio (version 1.1.456).

Results: Whole exome sequencing and HLA allele prediction was performed on 43 patients, 40 unrelated and 3 siblings.  All were ethnically Irish with a female:male ratio of 2.9:1, 88% had multifocal disease and 51% required a second-line agent for treatment. Psoriasis was present in 18.6% of patients a further 18.6% of 1^st/2^nd degree relatives.  HLA class I prediction was successful in all patients. HLA-B*27:05 was present in 17.5% of patients compared to 6% of the Irish population (OR 3.28, 95%CI 1.18 – 7.8,  p=0.011). Patients carrying HLA-B*27:05 allele did not have more frequent co-morbidity with HLA-B*27 associated diseases than the overall cohort.  HLA-C*06:02 was present in 27.5% of patients compared to 17.5% (OR 1.96, 95% CI p=0.13).  Patients carrying HLA-C*06:02 were not significantly associated with a personal or family history of psoriasis.  All other alleles were found at frequencies close to the Irish population frequency.

Conclusion: There is a statistically significant association between the Irish CNO population and HLA-B*27:05 allele known to be associated with inflammatory diseases such as enthesitis-related arthritis.  Results need to be replicated in a larger cohort for further stratification to be possible.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/chronic-nonbacterial-osteomyelitis-is-associated-with-hla-b27/