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Accurate identification of antibody reactivity against HLA-DQ antigens was difficult by using the old serological assays because of the strong linkage disequilibrium between HLA-DR and HLA-DQ (the usual inheritance of a certain HLA-DR molecule that ties together with the same DQ molecule within a racial group). The accurate and precise identifications of anti-HLA-antibodies of DQ specificities were made possible with the introduction of multiplex-bead arrays (Luminex), using single antigen bead (SAB) assay. The SAB assay is also considered today to be the most sensitive and specific method for alloimmunization assessment even for the low titer anti-HLA-antibodies. However, it is becoming clear that the detection of the HLA antibodies by SAB is not absolutely perfect due to the variation in densities, conformations and orientations of the antigen coated beads. Unlike HLA-DR, the HLA-DQ antigens are made of two polymorphic chains, both (alpha and beta chains) can contribute to the process of immunization individually or jointly. Routine SAB testing approach, which assigns the specificities based on beta chains and ignores the contribution of the DQα chains, can lead to erroneous DQ-antibody assignments. Therefore, it is important to recognize both the peculiarity of the HLA-DQ antigens as well as the nature of the assay format used in order to reach the correct antibody assignments. Erroneous donor specific antibodies (DSA) assignment may lead to denial of an otherwise immunologically compatible organ transplant, or exposing transplant recipients to unnecessary investigations or immunosuppression. The following two patients presented with HLA-antibodies against DQ antigens (anti-DQ-Abs) highlight these two scenarios., (Copyright © 2015 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

Definition of sensitization to class II antigens based on its β chain may be problematic for DQ due to the polymorphism of both α & β chains in DQ antigens and can wrongly assigned DSA that may decline immunologically compatible transplant. The patient presented here highlights this problem A 23-year-old male referred for kidney transplantation. HLA-typing for him and three living related potential donors are summarized below. A B C DRB1 DQA1 DQB1 Pt 02, 33 49, 51 07, 15 17, 16 05:01, 01:02 02:01, 05:02 D1 11, 68 35, 51 04, 15 04, 11 03:02, 05:05 8, 7 D2 01, 03 51 06, 16 04 03:01 8 D3 01, 31 35, 51 06, 07 17, 04 03:01, 05:01 8, 02:01 HLA-antibodies by SAB were positive for DQ7–9. Flow XM with donor 1&2 (D1, D2) were positive for B-cells but negative with donor 3 (D3). A closer analysis of SAB data (Fig. 1) revealed positive reactivity of all DQ8 coated beads except bead no. 82. DQA1 ∗ 03:02 was thought then contributing to the positivity. High resolution typing (HR) for DQ8 confirmed sharing of DQA1 ∗ 03:02, DQB1 ∗ 03:02 between D1&2. Reactivity analysis for bead no. 42 and 43 could not exclude positivity to DQ8 β (B ∗ 03:02) component due to negative reaction of the corresponding α components. Furthermore, the combination DQA ∗ 03:01, DQB ∗ 03:02 coated beads (present in D3) reacted strongly. Flow PRA class II bead on BD analyzer, showed positive DQA1 ∗ 03:02 homozygous bead only. DQA1 ∗ 03:02 homozygous present in D2 & a single copy of this allele present in D1, while D3 does not carry this allele, so we concluded that actual antigenic epitopes is located in DQA1 ∗ 03:02, possibly the homozygous conformation increased its expression & contributed to the higher channel shift of the FXM with D2. Due to uncertainty in assessing the immunological risk the transplant was denied several times before the patient underwent uneventual transplant from D3 and continued enjoying good kidney function up to one month post transplant. [ABSTRACT FROM AUTHOR]