Seronegative autoimmune diseases: A challenging diagnosis

Area of Science:

• Immunology
• Clinical Medicine
• Pathology

Background:

• Autoimmune diseases (AID) represent a significant global health burden, affecting over 100 distinct conditions.
• Early diagnosis of AID is crucial for preventing complications and optimizing patient management.
• Autoantibodies are key diagnostic markers for most AID, aiding in early and pre-clinical detection.

Purpose of the Study:

• To critically review the causes of seronegative autoimmune diseases (AID) where autoantibodies are absent.
• To discuss the diagnostic challenges and management implications for seronegative AID.
• To examine seronegativity across various autoimmune conditions, including autoimmune gastritis, celiac disease, and rheumatoid arthritis.

Main Methods:

• Narrative review of existing literature on seronegative autoimmune diseases.
• Analysis of potential determinants of seronegativity, such as suboptimal laboratory tests and immunosenescence.
• Examination of diagnostic strategies beyond autoantibody detection, including clinical assessment and histopathology.

Main Results:

• Seronegative AID occurs in a minority of patients due to factors like test inaccuracy, immunosuppression, or immunosenescence.
• Diagnosis of seronegative AID is complex, often requiring a combination of clinical evaluation, histopathology, and radiological tests.
• Understanding seronegativity is vital for accurate diagnosis and management across a spectrum of autoimmune disorders.

Conclusions:

• Seronegative AID presents unique diagnostic hurdles that necessitate a comprehensive approach.
• Further research into the mechanisms and improved diagnostic tools for seronegative AID is warranted.
• This review highlights the importance of considering seronegativity in the clinical workup of suspected autoimmune diseases.