From the Guidelines
High IgG with normal IgA and IgM and normal C3 and C4 levels alone is not sufficient to indicate lupus. This is because elevated IgG can be seen in various conditions, including chronic infections, other autoimmune diseases, and certain malignancies, as noted in the context of monitoring patients with systemic lupus erythematosus 1. The diagnosis of lupus (systemic lupus erythematosus or SLE) requires a combination of clinical and laboratory criteria, including specific symptoms, physical examination findings, and laboratory tests such as anti-nuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), and anti-Smith antibodies, along with evidence of immune-mediated organ involvement. Key points to consider in the diagnosis and management of lupus include:
- Assessment of disease activity and organ damage, as recommended by guidelines for monitoring patients with SLE 1.
- Evaluation of comorbidities, including cardiovascular risk factors and osteoporosis, which are crucial for the overall management of patients with SLE 1.
- Laboratory assessment, including the monitoring of autoantibodies and complement levels, such as ANA, anti-dsDNA, anti-Ro, anti-La, anti-RNP, anti-Sm, anti-phospholipid, C3, and C4, at baseline and during follow-up 1. Given the complexity of lupus diagnosis and the nonspecific nature of elevated IgG levels, a comprehensive evaluation by a rheumatologist is necessary if lupus is suspected, including a complete medical history, physical examination, and additional laboratory testing beyond immunoglobulin levels.
From the Research
Immunoglobulin Levels and Lupus Diagnosis
- High IgG levels with normal IgA and IgM levels can be found in patients with systemic lupus erythematosus (SLE) 2
- However, elevated IgG levels are not specific to SLE and can be found in other autoimmune diseases as well
- Normal C3 and C4 levels do not rule out SLE, as these levels can fluctuate during the course of the disease 3, 4
Complement Levels and Lupus Diagnosis
- Low C3 and C4 levels are often associated with active SLE, but normal levels do not exclude the diagnosis 3, 4
- The British Isles Lupus Assessment Group (BILAG) index and the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) are used to assess disease activity in SLE, and take into account various clinical and laboratory parameters, including complement levels 4
Antinuclear Antibody Testing
- Antinuclear antibody (ANA) testing is a key diagnostic tool for SLE, but a positive result is not specific to SLE and must be interpreted in the clinical context 5
- ANA staining patterns and specific autoantibody testing can help diagnose SLE or ANA-associated diseases 5
IgG Subclass Deficiency and Lupus
- Hydroxychloroquine therapy has been shown to have no significant effect on IgG, IgG subclass, IgA, or IgM levels in women with IgG subclass deficiency and SLE, Sjögren syndrome, or rheumatoid arthritis 6
- However, this study did not specifically address the question of whether high IgG with normal IgA and IgM and normal C3 and C4 indicates lupus.