Background: The objective of the study was to examine the interrelationships and clinical significance of IgA red cell antibodies in the autoimmune response.
Study design and methods: The records of 5235 patients referred to an immunohematology center over a 14-year period were critically examined for patients who had IgA autoantibodies, defined as elutable IgA immunoglobulins that would rebind to normal cells.
Results: One hundred twenty-four patients (61 male) aged 6 to 98 years had warm-reacting IgA autoantibodies. In 75 individuals, these were idiopathic; neoplasms were the most common associated conditions in the individuals with secondary IgA autoantibodies. IgA was the only immunoglobulin present in 6 patients; all others also had IgG and/or IgM coating their cells, and 102 individuals also had increased amounts of cell-bound complement. In a comparison by chi-square test of populations with haptoglobins of < 0.1 g per L, IgA was shown to act synergistically with IgG in producing hemolysis (p < 0.01).
Conclusion: Autoimmune hemolysis due to IgA antibodies alone in rare, with red cell destruction occurring through mechanisms similar to those for IgG. Most commonly, IgA acts synergistically with other immunoglobulins (usually IgG) and complement; the hemolysis may be severe. Whether IgA autoantibodies alone can activate complement remains controversial, but increasing evidence suggests that they can, possibly via the alternative pathway, and that this activation may result in intravascular hemolysis.