What does an elevated Immunoglobulin A (IgA) level of 165 indicate?

What Does an IgA Level of 165 Mean?

An IgA level of 165 mg/dL is mildly elevated and should prompt evaluation for alcoholic liver disease, chronic mucosal inflammation (including inflammatory bowel disease), IgA nephropathy, or IgG4-related disease, depending on your clinical context. 1

Understanding the Normal Range

• Normal serum IgA comprises approximately 15% of total immunoglobulins, with typical reference ranges varying by laboratory but generally falling between 70-400 mg/dL in adults. 2
• An IgA of 165 mg/dL represents a mild elevation above the lower-normal range, which is clinically significant when interpreted alongside other laboratory findings and clinical features. 1

Primary Diagnostic Considerations

Alcoholic Liver Disease (Most Common)

• Elevated IgA with elevated transaminases strongly suggests alcoholic steatohepatitis rather than autoimmune hepatitis. 1
• The pattern of immunoglobulin elevation is diagnostically useful: isolated IgA elevation points toward alcoholic liver disease, whereas isolated IgG elevation suggests autoimmune hepatitis, and isolated IgM elevation indicates primary biliary cirrhosis. 1
• Check for AST/ALT elevation with AST:ALT ratio >2:1, which is characteristic of alcoholic hepatitis. 1
• Alcohol cessation is the primary intervention if this diagnosis is confirmed. 1

IgA Nephropathy

• Elevated serum IgA may indicate IgA nephropathy, particularly when accompanied by hematuria or proteinuria. 1
• This is the most common primary glomerulonephritis worldwide. 1
• Check urinalysis for microscopic hematuria and obtain urine protein-to-creatinine ratio. 1
• Refer to nephrology for potential kidney biopsy confirmation if urinary abnormalities are present. 1

Chronic Mucosal Inflammation

• Persistent mucosal inflammation from chronic infections or inflammatory bowel disease can elevate IgA. 1
• Consider inflammatory bowel disease in patients with elevated IgA levels and chronic diarrhea or malabsorption. 1
• IgA plays a crucial role in maintaining mucosal barrier integrity in the respiratory and gastrointestinal tracts. 3, 4

IgG4-Related Disease

• Approximately 10% of patients with IgG4-related disease have elevated serum IgA levels. 5
• These patients show higher C-reactive protein levels, lower relapse rates, and better response to glucocorticoids compared to IgG4-RD patients without elevated IgA. 5
• Consider this diagnosis if there are features of autoimmune pancreatitis, retroperitoneal fibrosis, or other IgG4-RD manifestations. 5

Critical Diagnostic Algorithm

Step 1: Check liver enzymes (AST, ALT, alkaline phosphatase)

• If elevated with AST:ALT >2:1 → evaluate for alcoholic liver disease. 1
• If elevated with isolated IgG elevation → consider autoimmune hepatitis. 1

Step 2: Obtain urinalysis and urine protein-to-creatinine ratio

• If hematuria or proteinuria present → refer to nephrology for IgA nephropathy evaluation. 1

Step 3: Assess for gastrointestinal symptoms

• If chronic diarrhea, malabsorption, or abdominal pain → consider inflammatory bowel disease workup. 1

Step 4: Check IgG and IgG4 levels

• If IgG4 elevated with organ involvement → evaluate for IgG4-related disease. 5

Important Caveats and Pitfalls

• Do not dismiss mildly elevated IgA as clinically insignificant—even modest elevations can signal underlying pathology requiring intervention. 1
• High immunoglobulin levels, including IgA, are associated with increased all-cause mortality and infectious disease mortality, suggesting they may signal subclinical disease. 6
• IgA deficiency (levels <7 mg/dL) is associated with autoimmune diseases, but elevated IgA can also occur in autoimmune conditions, particularly IgG4-related disease. 7, 5
• When using IgA-based antibody tests (such as tissue transglutaminase for celiac disease), always measure total IgA to avoid false-negative results from IgA deficiency. 1
• Medication use should be investigated, as certain drugs can affect immunoglobulin levels. 8

When to Refer

• Nephrology: If urinary abnormalities (hematuria, proteinuria) are present with elevated IgA. 1
• Gastroenterology: If liver enzyme abnormalities or chronic gastrointestinal symptoms accompany elevated IgA. 1
• Rheumatology: If features of IgG4-related disease or other autoimmune conditions are present. 5