BACKGROUND: The objective of the study was to examine the interrelatio
nships and clinical significance of IgA red cell antibodies in the aut
oimmune response. STUDY DESIGN AND METHODS: The records of 5235 patien
ts referred to an immunohematology center over a 14-year period were c
ritically examined for patients who had IgA autoantibodies, defined as
elutable IgA immunoglobulins that would rebind to normal cells. RESUL
TS: One hundred twenty-four patients (61 male) aged 6 to 98 years had
warm-reacting IgA autoantibodies. In 75 individuals, these were idiopa
thic; neoplasms were the most common associated conditions in the indi
viduals with secondary IgA autoantibodies. IgA was the only immunoglob
ulin present in 6 patients; all others also had IgG and/or IgM coating
their cells, and 102 individuals also had increased amounts of cell-b
ound complement. In a comparison by chi-square test of populations wit
h haptoglobins of <0.1 g per L, IgA was shown to act synergistically w
ith IgG in producing hemolysis (p<0.01). CONCLUSION: Autoimmune hemoly
sis due to IgA antibodies alone is rare, with red cell destruction occ
urring through mechanisms similar to those for IgG. Most commonly, IgA
acts synergistically with other immunoglobulins (usually IgG) and com
plement; the hemolysis may be severe. Whether IgA autoantibodies alone
can activate complement remains controversial, but increasing evidenc
e suggests that they can, possibly via the alternative pathway, and th
at this activation may result in intravascular hemolysis.