I have seen both auto anti-Ena and alloanti-Ena. Anti-Ena can be IgM or IgG. Alloanti-Ena is an exceptionally rare antibody. The few examples I have seen have been associated with hybrid glycophorins, not with the extremely rare Mk type. A clue for a hybrid in such a case is usually only M or N plus S or s are present, but we had a TSEN homozygote (probable) come our way and her RBCs typed M+N-S-s-U+ and the antibody was anti-EnaFR. The antibody was reactive with all RBCs, except the autologous RBCs, in the indirect antiglobulin test with PEG-IgG (nonreactive in a short room temp incubation) and with ficin-treated RBCs at 37C and AHG. The antibody also reacted with DTT-treated RBCs in LISS-IgG. Rare RBCs, including null phenotypes, for specificities that are not denatured by ficin and DTT were tested to attempt to determine the specificity. The MNS typing, combined with an Hispanic ethnicity was a clue in this case that we might be dealing with an hybrid (we don't expect S-s- for individuals other that Blacks, but learn to expect the unexpected!). The patient's serum was nonreactive with two examples of RBCs from individuals with hybrids. Adsorptions were used to complete exclusion of common alloantibodies. The New York Blood Center completed the investigation into the hybrid part with immunoblots for us. One of the difficulties with proving anti-EnaFR is that anti-Wrb may also be present since Wrb requires the presence of GPA. I am only aware of one example of RBCs that are Ena+;Wr(b-). The few examples of anti-Ena associated with hybrids that I have seen had anti-EnaFR/-Wrb in the serum. By the way, there is no donor blood available I have also seen autoanti-Ena, both autoanti-EnaFR and autoanti-EnaFS, also reactive only at the antiglobulin test. Again, all RBCs are reactive, including the patient's RBCs. Here, since this is not because of a missing normal GPA, the MNS typing is noninformative. I suspect that autoanti-EnaFR is most often not recognized because it looks just like an idiopathic IgG warm autoantibody. Autoanti-EnaFS, however, does not react with ficin-treated RBCs. The serologic problem here is to distinguish anti-EnaFS from autoanti-Pr, which is also nonreactive with ficin-treated RBCs. (Autoanti-Ge also need to be excluded). While I was taught that anti-Pr is a cold reactive antibody, there are examples of warm reactive anti-Pr. Jumping through some hoops, these two specificities can be readily distinguished by testing with neuraminidase-treated RBCs. Check Issitt and Anstee, Applied Blood Group Serology (or Issitt's earlier editions) for details - remeber neuraminidase-treated RBCs react with anti-T in most sera! Defining an autoantibody specificity, however, is purely of academic interest. Nonreactivity with ficin-treated RBCs is not typical of warm autoantibodies, so it gets our attention. Sorry for the long post. Anti-Ena is not a simple antibody!