Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the joints. It is associated with progressive disability due to joint deformation and systemic complications. A casual link between gluten sensitivity and RA has been previously described and dietary manipulation is commonly used in RA patients, leading us to investigate whether gluten sensitivity is associated with severity of RA symptoms. Three major types of gluten sensitivity are Celiac disease (CD), non-celiac gluten sensitivity (NCGS) and wheat allergy (WA/Non Celiac Wheat Sensitivity). CD is a T cell- and B cell-mediated autoimmune disease and has been previously associated with RA. NCGS patients report intestinal and extra-intestinal symptoms shortly after ingesting gluten, however the cause is not known. WA is a true allergic reaction to proteins contained in wheat and grains. Neither NCGS nor WA has been previously associated with RA in large cohort, well-controlled studies.
The objectives of this grant proposal are to identify the frequency of CD, NCGS and WA in patients with RA. Further, we will evaluate the correlation of clinical symptom severity of RA patients with gluten sensitivity or WA.
To test this hypothesis we propose two Specific Aims:
Specific Aim 1: To identify a subpopulation of RA patients that have IgG-mediated or IgA-mediated gluten sensitivity. We will test serum samples from RA patients with a panel of CD diagnostic markers and inflammatory biomarkers. The results from these analyses will elucidate the number of RA patients in our study with gluten sensitivity arising from CD or NCGS. Results from serum analyses will be compared to RA patient symptom severity. The results from this Specific Aim will help identify a link between RA symptom severity and CD or NCGS.
Specific Aim 2: To identify a subpopulation of RA patients that have IgE-mediated wheat allergy. We will test serum samples from RA patients for the presence of total and wheat-specific IgE antibodies. The results from this analysis will elucidate the number of RA patients in our study with a true IgEmediated wheat allergy, as opposed to sensitivity to wheat or gluten. Results from these serum analyses will be compared to RA patient symptom severity. The results from this Specific Aim will determine whether RA symptom severity is associated with wheat-specific allergy.
The results from our study have the potential to widely impact the standard of care for RA patients and provide support for screening and diet modification in this population.