Autoantibodies to Gastric Parietal Cells in Rheumatoid Arthritis Patients

Keesler Air Force Base Medical Center125 enrolled

Overview

A review of the literature reveals that very few studies have assessed the potential co-existence of vitamin B12 deficiency due to gastric parietal cell autoantibodies. While Segal et al. in 2004 published a study which found that 49% of patients with RA had vitamin B12 deficiency, no assessment of the etiology or the presence of autoantibodies was made. While Goeldner et al. in 2011 and Datta et al. in 1990 demonstrated that anti-gastric parietal cell antibodies (anti-GPC Ab) were found in \<5% to 28% of RA patients respectively, no additional testing was implemented to determine the significance, specifically whether or not the presence of anti-GPC Ab related to vitamin B12 deficiency. The purpose of this study is to determine the prevalence and metabolic significance of anti-GPC Ab in three cohorts: (1) a group of patients with Rheumatoid Arthritis, (2) a group of patients with autoimmune thyroid disease (AITD), and (3) a group of patients with neither RA or AITD. To determine the significance of the presence of anti-GPC Ab, testing of the current serum B12 level along with a metabolite dependent on adequate vitamin B12 levels (Methylmalonic acid) will be tested.

Background: Organ specific antibodies such as anti-gastric parietal cell antibodies (anti-GPC Ab) have been found in a variable number of patients with RA, but it is unclear what significance these antibodies have on actual vitamin B12 levels. Patients with RA have been found to have vitamin B12 deficiency up to near 50% but it is unclear if this deficiency is due to anti-GPC Ab. Hypothesis: By virtue of the aberrant autoimmune process that occurs in RA, patients with RA are more likely to have anti-GPC Ab and more likely than a control arm or participants with autoimmune thyroid disease (AITD) to have vitamin B12 deficiency. Method: 135 patients will be consented; 45 to the RA arm, 45 to an AITD arm, and 45 to a control arm. Exclusion criteria will filter patients who would have other reasons for altered vitamin B12 absorption, such as inflammatory bowel disease, surgery, or medication use. After obtaining consent subjects will be sent to lab a serum anti-GPC Ab test (obtainable in an SLE panel), RF, B12/folate (as available for ordering in CHCS), methyl malonic acid, and (for the control arm subjects and AITD subjects) an anti-CCP IgG. Patients will also complete a one-sided, one page questionnaire asking them about dietary and medication exposures. Outcomes: (1) Determine whether evidence of serum vitamin B12 deficiency, as measure by either a low vitamin B12 level or elevated methylmalonic acid, will be more common in RA patients with anti-GPC Ab. (2) Determine the prevalence of anti-GPC Ab in a group of patients with RA as compared to a group of patients with AITD and with no known systemic or organ specific autoimmune condition.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Adult, age 18 and older * RA arm: History of Rheumatoid Arthritis * AITD arm: History of an autoimmune thyroid disease without a history or clinically obvious manifestation of an organ specific or systemic autoimmune process. * Control arm: No history of RA and no history or clinically obvious manifestation of an organ specific or systemic autoimmune process. Exclusion Criteria: * Known vitamin B12 deficiency for which the participant was formerly treated or continues to receive therapy. * Active malabsorptive state to include but not limited to celiac disease, inflammatory bowel disease, etc. * Surgically induced malabsorptive state to include but not limited to Roux-en-Y Gastric bypass * Use of medications that may interfere with vitamin B12 absorption * Patients with a thyroid condition not consistent with an autoantibody process (i.e. congenital absence of the thyroid, infectious thyroiditis, thyroidectomy for non-autoimmune process, toxic multinodular goiter) will be excluded from the autoimmune thyroid arm.

Outcomes

Primary Outcomes

Prevalence of Vitamin B12 Deficiency

Hypothesis: Evidence of serum vitamin B12 deficiency, as measure by either a low vitamin B12 level or elevated methylmalonic acid, will be more common in RA patients with anti-GPC Ab.

Time frame: 7 months

Secondary Outcomes

Presence of Anti-GPC Antibodies

Hypothesis: Evidence of anti-GPC Ab in a group of patients with RA will be more prevalent as compared to a group of patients with AITD and with no known systemic or organ specific autoimmune condition.