The autoimmune-associated single nucleotide polymorphism within PTPN22 correlates with clinical outcome after lung transplantation

K. Budding, J. van Setten, E.A. van de Graaf, O.A. van Rossum, T. Kardol-Hoefnagel, E.J.D. Oudijk, C.E. Hack, H.G. Otten

Chair(s): Drs. K.C.A. Geneugelijk & prof. dr. C. van Kooten

Thursday 9 march 2017

14:42 - 14:54h at Hendrik Marsmanzaal

Categories: Parallel - Basaal

Parallel session: Parallelsessie XV - Basaal - Moleculaire analyses en het adaptieve immuunsysteem in orgaantransplantatie

Obstructive chronic lung allograft dysfunction (BOS) is the major limiting factor for lung transplantation (LTx) outcome. Both T cell an B cell mediated autoimmunity contribute to the development of autoantibodies associated with the development of chronic rejection. PTPN22 is described as the hallmark autoimmunity gene, and one specific single nucleotide polymorphism (SNP), rs2476601, is associated with multiple autoimmune diseases, impaired T cell regulation and autoantibody formation. Taking into consideration the contribution of autoimmunity to LTx outcome, we hypothesized that polymorphisms in the PTPN22 gene could be correlated to BOS incidence. Therefore, we identified six selected SNPs within PTPN22 and analyzed both patient and donor genotypes on BOS development post-LTx. A total of 145 patients and matched donors were included, and individual SNPs and haplotype configurations were analyzed. We found a significant association between patients carrying the heterozygous configuration of rs2476601 and a higher risk for BOS development (p=0.005, OR: 4.400, 95%CI: 1.563–12.390). This was confirmed via Kaplan-Meier analysis which showed that heterozygous patients exhibit a lower BOS-free survival compared to patients homozygous for rs2476601 (p=0.0047). Furthermore, one haplotype, which solely contained the heterozygous risk variant, was associated with BOS development (p=0.015, OR: 7.029, 95%CI: 1.352–36.543).

Our results show that LTx patients that are heterozygous for SNP rs2476601 are more susceptible for BOS development and indicate a deleterious effect of the autoimmune-related risk factor of PTPN22 in patients on LTx outcome.