Jr is a high-prevalence red blood cell (RBC) antigen. The clinical significance of anti-Jr is still not well established because it occurs rarely and has only been evaluated in few cases, but generally is thought to be of little relevance in the development of hemolytic disease of the fetus and newborn (HDFN). However, anti-Jr has been reported as a cause of mild HDFN and, recently, a case of fatal HDFN associated with anti-Jr was published. We describe a fatal immune HDF possibly due to anti-Jr. A 39-year-old Caucasian woman was referred to our hospital in the 12th week of pregnancy. A routine ultrasonography examination showed hidrops fetalis. The obstetric history of this patient included four pregnancies before the current one. The first pregnancy was in 1997 and ended in abortion, but the antibody screening test (AST) was not performed. In 1998 and with the second pregnancy, an AST revealed an antibody of a high-incidence RBC antigen (Makropanel 16, Amsterdam, Netherlands; Panocell10, Immucor Gamma, Norcross, CA; DiaMed, Morat, Switzerland) by column agglutination Diana Gel (Group Grifols, Barcelona, Spain). This antibody was studied in a reference laboratory (American Red Cross, Los Angeles, CA) and an anti-Jr (titer <8) was identified. The antibody subclass was immunoglobulin G (IgG)4 and the monocyte monolayer assay (MMA) was normal (7%) by the method described by Nance and coworkers. Beside this pregnancy, she had two more in 2000 and 2004, but none of the three babies had anemia, even if all had positive DAT (2+) and the elution showed anti-Jr (Gamma Elu-Kit II, Immucor Gamma; titer <16). The IgG subclass and MMA were not performed at that time. In the fifth pregnancy (2008), the ultrasound examination showed hidrops fetalis with no congenital anomaly. The titer of anti-Jr had increased to less than 128 and the IgG predominant subclasses were IgG2 and IgG3, performed with murine monoclonal antibodies (Peli Class human IgG subclass kit, Sanquin Reagents, Amsterdam, Netherlands). The result of the MMA with maternal serum and Jr(a+) RBC was 15 percent (control value, 7%). Serologic tests to rule out infectious causes of anemia were all negative (IgM parvovirus B19, IgM varicela-zoster, IgM rubeola, IgM Epstein-Barr, IgM toxoplasma, VHC, and VHB). The anti-phospholipid, anti-DNA, anti-nuclear, and anti-cardiolipin antibodies were also negative. The pregnancy ended in a voluntary abortion because of the little viability of the fetus. Although anti-Jr is not a common cause of HDFN, there are many data that suggest its involvement in this case, such as previous pregnancies, positive DAT in the newborns, identification of anti-Jr in their eluates, increased titer of anti-Jr, positive MMA, IgG subclasses, and the absence of other causes that could explain hidrops fetalis. A review of the literature indicates that anti-Jr may be clinically significant, because it has been related to some cases of HDFN. Most cases are mild or moderate, but some severe and fatal cases have been recently reported. This case provides more information about the clinical significance of anti-Jr as a cause of HDFN, which can have a fatal outcome. Therefore, and according to other authors, we recommend close monitoring of pregnant women with high or increasing titers of anti-Jr, especially those with previous pregnancies. Francisco Arriaga, MD e-mail: arriaga_fra@gva.es Ines Gomez Maria Dolores Linares Adriana Gascon Nelly Carpio Blood Bank Hematology Department Alfredo Perales Obstetric Service Hospital Universitario La Fe Valencia, Spain