| Popis: |
Background: High levels of neutralizing Granulocyte-Macrophage Colony Stimulating Factor auto-antibodies (GM-CSF Ab) in Crohn’s Disease (CD) are associated with ileal involvement, stricturing behavior, and surgery. Single-nucleotide polymorphisms (SNPs) in Janus Associated Kinase 2 (JAK2) and Signal Transducers and Activators of Transcription 3 (STAT3) increase risk for CD, and these genes are involved in regulation of lymphocyte functions including antibody production. The association between carriage of risk alleles in JAK2/STAT3 and serum GM-CSF Ab concentration was investigated. Methods: Genotyping for JAK2(rs10758669), and STAT3(rs744166) was performed and serum GM-CSF Ab concentrations (ELISA) were measured in 302 pediatric CD patients and 174 healthy controls. CD patients who carried at least one risk allele were classified as JAK2+ or STAT3+. Results: The median(IQR) serum GM-CSF Ab concentration increased from 1.3(0.4, 6.3) mcg/mL in JAK2+ CD patients to 2.0(0.6, 9.0) in JAK2- CD patients (p=0.04). The median serum GM-CSF Ab concentration was also increased in STAT3+ CD patients. Serum GM-CSF Ab did not vary with JAK2 or STAT3 risk allele carriage in healthy controls. When considering each of the four possible JAK2:STAT3 combined genotypes, the highest serum GM-CSF Ab concentration (2.12(0.7, 9.7) mcg/mL) was observed in patients who were JAK2- and STAT3+ (34% of the group), p=0.023 by Kruskal-Wallis test. Regression models which included age, gender, disease location and behavior, and medication exposures confirmed a strong association between the JAK2-STAT3+ genotype and serum GM-CSF Ab level. Conclusions: Genetic variants in JAK2 and STAT3 which increase risk for CD are associated with serum GM-CSF Ab concentration. |
