Research article: Autoimmune Disease-Associated Reference Intervals for Routine Laboratory Tests Among Adult Outpatients

Landon J. Stovall-Guthrie, Juan U Rojo, Renée E. Lastrapes, Rajkumar Rajendran

Abstract

Chronic kidney disease (CKD) is a growing public health challenge with substantial morbidity, mortality, and cost. Early detection is critical, yet abnormal kidney function results in primary care are often lacking timely follow-up.

Background: Current health-associated reference intervals (RIs) used in clinical practice are less applicable in patients with autoimmune diseases, creating the need for RIs aligned with the patient population. This study identified autoimmune disease-associated RIs and compared them to gold-standard RIs using analytical and biological variation.

Methods: Retrospective data for 16 laboratory tests were collected on outpatients with diagnosis codes for 5 autoimmune diseases (rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), ulcerative colitis (UC), Crohn’s disease (CD), and Hashimoto’s thyroiditis (HASHD) to establish RIs, using the Clinical Laboratory Science Institute guidelines. The reference population delta was calculated between disease-associated and health-associated RIs to determine significance based on a defined critical z score.

Results:  Of the 1,023 patient records reviewed, most were white (85%, n = 848) females (80%, n = 818) between the ages of 45 and 64 (44%, n = 451). Rheumatoid arthritis (RA) was the most prevalent condition (43%, n = 437). Separate RIs were established for the populations based on sex, age, and ethnicity. Statistically significant RIs included: SLE-associated changes in red blood cells (RBC’s), hemoglobin, and lymphocyte counts in females; SLE-associated albumin levels in diabetic patients; RA-associated hemoglobin in black, white, and older females; RA-associated RBC counts in males and females with cardiovascular disease; UC-associated changes in RBC, hemoglobin, and chloride in males; CD-associated hemoglobin in both sexes; CD-associated platelet count in males; and HASD-associated hemoglobin in females.

Conclusions: The autoimmune diseases impact chloride, RBC, hemoglobin, platelet, and lymphocyte RIs, suggesting the respective disease-associated RIs could be used to improve laboratory-based clinical decisions.

Keywords: Confidence interval, systemic lupus erythematosus, ulcerative colitis, white blood cell, red blood cell, Hashimoto’s thyroiditis, autoimmune thyroiditis, rheumatoid arthritis, alanine transaminase, aspartate transaminase, Crohn’s disease.

Int. J. Bio. Lab. Sci 2026(15)1:36-58 【PDF】