|Year : 2020 | Volume
| Issue : 3 | Page : 132-134
Bombay and Lewis phenotype testing in correlation with leukocyte adhesion deficiency type II: The blood bank's role in diagnosis
Khalid Batarfi, Ahmed Maded Al Harbi, Bryan Rosario, Abdullah Al Enazi, Paolo Domingo Kiseo
Department of Pathology and Laboratory Medicine, King Abdullah Specialist Children Hospital, King Abdulaziz Medical City-CR, Ministry of National Guard, Riyadh, Saudi Arabia
|Date of Submission||12-Dec-2019|
|Date of Decision||23-Feb-2020|
|Date of Acceptance||05-Jun-2020|
|Date of Web Publication||16-Sep-2020|
Mr. Ahmed Maded Al Harbi
Department of Pathology and Laboratory Medicine, King Abdullah Specialist Children Hospital, King Abdulaziz Medical City-CR, Ministry of National Guard, Riyadh
Source of Support: None, Conflict of Interest: None
Leukocyte adhesion deficiency type II (LAD II) is a rare hereditary disorder caused by the mutation in the guanosine diphosphate-fucose transporter gene (SLC35C1). LAD II is characterized by inexpression of ABO antigens (i.e., Bombay phenotype) and the lack of Lewis red blood cell (RBC) antigens. In addition to high neutrophil counts, patients also manifest recurrent infections with developmental delays and stunted growth. Blood bank laboratory tests such as blood grouping, RBC phenotyping, antibody screening and identification of the nature of the antibody were conducted in order to confirm the consequences associated with this gene anomaly in this case report. Type and screen results initially identified the patient as group “O” Rh positive with pan-reactive antibody screening cells and identification panel cells. The patient plasma showed significant incompatibility to all O-positive donors' RBCs. The patient's RBCs were tested against anti-H lectin and Lewis (Lea, Leb) typing antisera and showed no reaction, which meant that the patient does not express neither Lewis antigens nor H antigen on his red cell. The presence of anti-H (in a Bombay phenotype individual) explained the reactivity to reagent red cells and crossmatched incompatibility of Group O units as these cells naturally contained the H antigen.
Keywords: Bombay blood group, fucose synthesis, leukocyte adhesion deficiency Type II, Lewis phenotype
|How to cite this article:|
Batarfi K, Al Harbi AM, Rosario B, Al Enazi A, Kiseo PD. Bombay and Lewis phenotype testing in correlation with leukocyte adhesion deficiency type II: The blood bank's role in diagnosis. J Appl Hematol 2020;11:132-4
|How to cite this URL:|
Batarfi K, Al Harbi AM, Rosario B, Al Enazi A, Kiseo PD. Bombay and Lewis phenotype testing in correlation with leukocyte adhesion deficiency type II: The blood bank's role in diagnosis. J Appl Hematol [serial online] 2020 [cited 2020 Sep 22];11:132-4. Available from: http://www.jahjournal.org/text.asp?2020/11/3/132/295126
| Introduction|| |
Leukocyte adhesion deficiency (LAD) is a very rare autosomal recessive condition which was first observed during the 1980s. This practically new and uncommon disease had only been defined in the 1990s, and only less than 10 cases had been described since its discovery. Remarkably, this disease is only presented with an equally rare blood group: the Bombay phenotype. Lewis antigens are also inexpressed as these blood group systems rely on effective fucose synthesis. As a distinct clinical manifestation, patients experience recurrent bacterial infections due to a defective White Blood Cell (WBC) adhesion resulting in ineffective chemotaxis, which leads to the inability to form pus and very high WBC counts (leukocytosis, neutrophillia). It is a syndrome wherein leukocytes are unable to adhere and migrate during inflammatory processes and defense reactions. Normally, leukocytes move through the bloodstream and “roll” along the endothelial wall and travel to target sites along the surrounding tissue, and these movements are regulated through primary adhesive integrin receptors. There are three types to this condition (LAD I, II, and III) depending on the defective integrin. LAD II, on the other hand, is the rarest, with less than ten patients being described. It is a milder form of the disease which has a compromised fucosyltransferase activity caused by loss of fucose synthesis. This leads to the nonexpression of the H antigens, ABO, and Lewis blood group antigens and poor formation of Sialyl-Lewisx, an L-selectin ligand necessary for cellular movement and chemotaxis. Only in LAD II, since the disease process involves the inability to properly synthesize fucose, results in the inexpression of ABH and Lewis blood group antigens that could be observed using routine blood banking techniques.
| Case Report|| |
A 13 months old Saudi boy was referred to the pediatric cardiology clinic at King Abdulaziz Medical City in Riyadh. He was diagnosed with severe peripheral pulmonary stenosis with moderate chronic pericardial effusion. Other significant medical histories and clinical observations include slight prematurity at birth (i.e., 35th week) with low birth weight (1.8 kg), mental retardation, facial dysmorphic features (depressed nasal bridge), hypospadias, and fever of unknown origin with high WBC count (leukocytosis an average of 35–50 × 109 L). The medical team's initial assessment and planning were urgent medical evaluation and further workup for immediate cardiac catheterization and open-heart surgery. Tests were conducted including basic ABO/Rh typing and antibody screening (T/S), and the patient was typed as Group O positive with a pan-reactive antibody screening. As a next step, antihuman globulin antibody identification and direct antiglobulin test (DAT) were done using solid-phase technique. The patient's plasma was positive to all antibody identification panel cells with a negative DAT result, which was at the time interpreted as probable clinically significant IgG alloantibody to a high-incidence antigen of unknown identity. Efforts were made to find compatible O-positive packed red blood cell (RBC) units for the surgery, but none within the inventory could be found using a complete crossmatch as the compatibility testing showed strong reactivity and significant incompatibility. Surgery had to be, therefore, canceled, and all orders for transfusion were put on hold. Further investigation was performed where the patient's RBCs were tested against anti-H, and it was negative in addition to that the patient's plasma was tested against A1 cells, A2 cells, B cells, and O cells and displayed strong agglutination (4+); this patient lacks the H antigen on the RBCs which accompanied by the presence of anti-H antibody in his plasma. Moreover, there was no agglutination in the autocontrol test (a mixture of the patient's cells and plasma). This means that the patient will be compatible with only Bombay blood group donor. In addition to the blood bank testing, a genetic study was conducted and the patient was found to be homozygous for a variant p. Thr295IIe in the SLC35C1 gene. This gene encodes a Guanine diphosphate-fucose (GDP-fucose) transporter that is found in the Golgi apparatus. Mutations in this gene result in congenital disorders of glycosylation type IIc leading to leukocytosis and recurrent infections. Hence, these findings confirmed that this patient blood group is Bombay blood group.
| Discussion|| |
The ABO blood group system is unique in such a way that antibodies will be produced naturally against the lacking antigen on red cells. ABO typing is done by forward grouping, accompanied by a reverse typing to confirm this activity. Routine typing would include testing the cells with A, B, and D (Rh) antisera on the forward, and testing the plasma with reagent A1 cells and B cells, but further investigation with H lectin was needed in this case to investigate the strong antibody reaction where no compatible RBC unit was found. The antibody screening and identification gave clues about the possible immunoglobulin (reacts best in cold and room temperature while IgG reacts at 37°C) present but could not rule out the definite antibody due to their panreactivity patterns. A simple procedure of testing the patient's cell with anti-H and his plasma against a panel of RBC with different ABO groups demonstrated that the patient lacked the H antigen one his RBCs and has anti-H in his plasma, which confirms the Bombay phenotype. In addition, the Lewis blood group typing results of the patient were found to be Le (a−b−). These results highly suggest the patient's suspected fucosylation deficiency, which can be related in this case to LAD II, where patients are unable to express H and Lewis antigens. The addition of the sugars N-acetylgalactosamine and D-galactose to the H structure results in the formation of the A and B antigens respectively. In the absence of the H antigen, these reactions cannot take place. Thus, the A and B antigens are not produced even if the A and B genes are present. People who lack the A, B, and H antigens in their blood produce anti-A, anti-B, and anti-H antibodies as a consequence. The absence of A and B antigens mimics the O blood group, but the presence of the anti-H antibody causes a cross-reaction with all blood types, including the O group blood, which carries the H antigen. Despite its rarity, the clinical significance of this condition must not be underestimated due to its role in causing transfusion reactions. If recurrent infections, persistent hyperleukocytosis, and severe mental and growth retardation are present in an individual with the Bombay blood group, we should consider the possibility of the rare diagnosis of LAD II.
| Conclusion|| |
The malfunction in the patient's SLC35C1 gene assumably prohibited the transport of GDP-fucose to be synthesized into its functional form. This prevented a cascade of activities, wherein fucosylation – an action necessary for brain development, red cell antigenicity, and leukocyte function – was not possible. Neutrophil inactivity, the absence of Lewis antigens plus the occurrence of the Bombay phenotype are all consequences of this genetic disorder. The diagnosis of LAD II was recognized through fundamental parallels in established clinical epidemiology, genetic studies, and routine immunohematology testing. There is a unique and strong correlation between the LAD II disorder, the Bombay phenotype, and the absence of Lewis antigen expression, which highly suggest that findings in this case are due to the diagnosed disorder and confirmed using anti-H tests done in the blood bank.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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