LAUSR

Dear Editor, I read the article titled “Direct Antiglobulin Test Positivity in Children With Acute Lymphoblastic Leukemia at Diagnosis” with interest.1 The presence of a positive direct antiglobulin test (DAT) without hemolysis in patients with acute lymphoblastic leukemia is reported, but the reason is not mentioned. A positive DAT without hemolysis suggests a false-positive DAT. We reported in a previous study that DAT was false positive in ten cases with various diagnoses and high IgG levels (three acute myeloblastic leukemia (AML), one juvenile myelomonocytic leukemia (JMML), two congenital neutropenia, two leishmaniasis, and two immune thrombocytopenic purpura (ITP) cases).2 The positive DAT disappeared when immunoglobulin (Ig) levels returned to normal. When compared with autoimmune hemolytic anemia (AIHA) patients with positive DAT, we found mild IgG and IgM elevation in only one of these patients (case 4). AIHA is a potentially fatal complication of mostly hemolytic malignancies (often B-cell leukemia and lymphoma).3 The main disorders and conditions resulting in a false-positive DAT although in vivo hemolysis has not developed and erythrocyte life has not been shortened are acute and chronic leukemia, malignant lymphoma, infections, intravenous immunoglobulin G (IV IgG) administration and immunodeficiencies.4,5 Some previous studies have reported a positive DAT without hemolysis in patients found to have high levels of other immunoglobulins, especially IgG.6,7 Multiple myeloma can also result in a positive DAT without hemolysis.8 Similarly, we found high levels of IgG and also IgM and/or IgA levels in our patients in one of our studies. We believed that the IgG elevation was due to the primary disorders, and none of the patients had signs of hemolytic anemia. Immunoglobulin levels decreased after the primary disorder was treated or the patient entered remission while DAT turned negative in parallel. The reason all eight of the cases mentioned by the authors in their article with false-positive DAT had B-cell ALL with no hemolysis indicates that levels of immunoglobulins and especially IgG could be high in these patients due to the reasons mentioned above. The main molecules involved in immunoglobulin synthesis and secretion are immunoglobulin heavy (H) and light chains (kappa (κ), lambda (λ)), interleukin (IL4,5), and which interleukin receptor (IL12R), adhesion molecules (P-selectin, leukocyte fonction-associated antigen 1 (LFA-1)) and activation molecules (mainly CD28CD80/CD86). Increased or decreased immunoglobulin levels can be seen in various disorders (mainly malignancies) that disrupt these structures (genetic and molecular) involved in immunoglobulin synthesis and secretion. The total immunoglobulin level (mainly IgG)