Most antibodies to blood group antigens react optimally at a pH range of 6.5–7.5, similar to that of normal plasma or serum. Some antibodies, however, including anti-M, react preferentially or exclusively in an acidic environment with a pH below 6.5. Antibodies with anti-M specificity often show dosage. They can be weakly reactive and even look like nonspecific reactivity at the antihuman globulin phase especially when immediate spin and/or room temperature testing is not part of routine screening. Acidification of serum or plasma may help to identify these antibodies as clinically insignificant versus as an unidentified antibody for which clinical significance is unknown.
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