Abstract

Introduction: Idiopathic or immune-thrombocytopenic purpura (ITP) is defined as a bleeding disorder with the hallmark of autoimmune mediated thrombocytopenia. ITP is a diagnosis of exclusion. Primary biliary cirrhosis (PBC) is a presumed autoimmune disease of the liver. Many nonhepatic autoimmune diseases are found in association with PBC, and may prompt initial presentation. Several case reports described the co-occurrence of ITP and PBC. In some PBC patients, autoantibodies against SOX13 can be detected. SOX13 has been identified as a transcription factor promoting gamma-delta T-cell development while opposing alpha-beta T cell differentiation. As ITP has been linked to the autoimmune bicytopenic Evans syndrome, which may present as autoimmune lymphoproliferative syndrome (ALPS) with the hallmark of increased alpha-beta double negative T-cells, we are interested in a potentially etiological role of molecular SOX13 sequence variations in ITP patients.

Material and methods: After obtaining informed consent from ITP patients (n=34) and their legal guardians to participate in the IRB approved study genomic DNA was extracted from peripheral blood samples. The complete coding region of SOX13 including the classical non-coding splice sites was amplified by PCR. The amplicons were screened for sequence variations by Denaturing High Performance Liquid Chromatography (DHPLC) after heteroduplex induction. All samples with aberrant DHPLC retention patterns were directly sequenced.

Results: Two rare heterozygous sequence variations in the coding region of SOX13 were detected in a total of 4 patients (12%): c.1603C>T (Pro534Ser) and c.1836 C>T (synonymous). Discussion: In a healthy cohort with European ancestry the heterozygous c.1603C>T (Pro534Ser) genotype was detected in 1.7% of individuals. In our cohort 6% of the ITP patients were heterozygous. 2.6% of individuals in a cohort of African-Americans and Caucasians carried the heterozygous genotype c.1836C>T (synonymous). 6% of the investigated ITP patients were heterozygous. A surprising high proportion (12%) of pediatric ITP patients carries one of two rare SOX13 sequence variations. The rare heterozygous genotypes are 3.5 (c.1603C>T) respectively 2.3 times (c.1836C>T) more common than in published non-ITP cohorts.

Conclusion: It seems possible, that rare alleles of SOX13 accumulate in pediatric ITP cohorts. Larger case-control sample studies are needed to verify the results. The rare genotypes could influence the alpha-beta versus gamma-delta T-cell balance in the studied pediatric ITP patients. Immunological studies of our cohort are necessary to evaluate this suggested association.

Disclosures: No relevant conflicts of interest to declare.

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