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Background Current blood-matching practices are challenging for patients with autoimmune hemolytic anemia (AIHA) because autoantibodies may interfere in hemagglutination assays. Blood group genotyping methods are an important complement to serology and allow the prediction of the phenotype from deoxyribonucleic acid (DNA) with high accuracy. Furthermore, technology for genotyping of red blood cell antigens in donor-recipient matching for blood group polymorphisms is moving into practice, mainly for patient groups with hemoglobinopathies. However, the routine use of antigen molecular matching for AIHA patients remains to be better determined. We hypothesized that performing the molecular matching between AIHA patients and blood donors could improve the selection of antigen-matched red blood cell units. Methods Using the blood-MLPA assay, we determined the blood group genotype from 198 donors and 24 AIHA patients and performed the RBC molecular matching between the two groups. Besides, using the hemagglutination technique we performed the RBC phenotyping for major blood group antigens of AIHA patients and compare the phenotyping with the genotyping results. Results: We were able to find RBC genotype-matched donors for 20/24 (83.3%) of our AIHA patients. From 118 phenotyping results, we found three (2.5%) discrepancies between the phenotype predicted by genotyping and the phenotype determined by serology. Conclusions In this study, our data indicate the real benefits of RBC genotyping for AIHA patients who usually present problematic immunohematological serologic reactions. Such a strategy may present information about additional RBC alloantibodies and reduce the potential risk of transfusion reactions.

Neonatal alloimmune neutropenia (NAIN) is caused by maternal alloimmunisation to fetal human neutrophil antigens (HNAs). This study investigated maternal HNA/HLA alloantibodies involved with NAIN and identified the frequency of NAIN in Brazilian neonates. Neonatal neutropenia (neutrophil count < 1.5 × 109 /L) was investigated in samples from 10,000 unselected neonates, resulting in 88 neutropenic newborns (NBs) and their 83 mothers. Genotyping was performed by PCR-SSP (HNA-1/-4) and PCR-RFLP (HNA-3/-5). Serologic studies were performed by GAT (granulocyte agglutination test), Flow-WIFT (white blood cells immunofluorescence test) and LABScreen-Multi-HNA-Kit (OneLambda®) (LSM). Neonatal neutropenia was identified in 88/10,000 (0·9%) NBs. Genotyping revealed 60·2% maternal-fetal HNA incompatibilities (31·8% for HNA-1; 14·8% for HNA-3; 15·9% for HNA-4; 21·6% for HNA-5). Serologic studies revealed 37·3% of mothers with positive results with at least one technique. The detected anti-HNA specificities were confirmed in eight positive cases related to HNA-1/-3 systems. In cases with maternal-fetal HNA-4/-5 incompatibility, no specific neutrophil alloantibodies were found but anti-HLA I/II were present. Anti-HNA-2 was not identified. This is a large Brazilian study which involved the investigation of antibodies against all five HNA systems in neutropenia cases and showed a frequency of NAIN in 8/10,000 neonates. Among the HNA antibodies identified, we highlight the anti-HNA-1d and anti-HNA-3b, antibodies unusual in alloimmunised women, and rarely related to NAIN cases.

The Band 3 is a red blood cell protein that carries the DiDescribe the frequencies of the DI*A and DI*B alleles and the Band 3 Memphis among blood donors, sickle cell disease (SCD) patients and Amazonian Indians.A total of 427 blood samples were collected and separated into three groups: 206 unrelated blood donors, 90 patients with SCD and 131 Amazonian Indians. We performed DI*A/B, normal Band 3 and Band 3 Memphis genotyping, using the Polymerase Chain Reaction Restriction Fragment Length Polymorphism (PCR-RFLP).The frequency of the DI*A/DI*A genotype was 0.5% in blood donors and it was not found in other groups. The frequency of the DI*A/DI*B was higher in Amazonian Indians (33.6%) and the frequency of the DI*B/DI*B was highest in blood donors (92.2%). All 105 individuals tested were positive for the presence of normal Band 3 and of these individuals, only 5/105 (4.8%) presented the Band 3 Memphis mutation.We observed a higher frequency of the DI*B allele in blood donors and a low frequency of the DI*A/DI*A genotype in all groups studied. The Band 3 Memphis was found in a higher frequency in the blood donor group. Our findings highlight the importance of analyzing different population groups to gain a better understanding of the genetic association of blood group antigens.

Background The screening ofTrypanosoma cruzi-infected blood donors using two serological techniques frequently leads to conflicting results. This fact prompted us to evaluate the diagnostic performance of four “in-house” immunodiagnostic tests and two commercially available enzyme-linked immunosorbent assays (ELISAs). Material and Methods One hundred and seventy-nine blood donors, whose screening for Chagas disease was doubtful, underwent three in-house ELISAs, one in-house immunoblotting test (TESA-blot), and two commercial ELISAs (bioMerieux and Wiener) in an attempt to define the presence or absence of infection. Simultaneously, 29 donors with previous positive results from three conventional serological tests and 30 donors with constant negative results were evaluated. Results The ELISA-Wiener showed the highest rate in sensitivity (98.92%) and the ELISA-bioMerieux, the highest specificity (99.45%), followed by the TESA-blot, which showed superior performance, with lower false-negative (2.18%) and false-positive (1.12%) rates. In series, the combination composed of the TESA-blot and ELISA-bioMerieux showed slightly superior performance, with trifunctional protein deficiency (TFP) = 0.01%. Conclusion Our study confirms the high sensitivity and specificity of commercial kits. To confirm the presence or absence of T. cruzi infection, the combination of TESA-blot and ELISA-bioMerieux may be suggested as the best alternative. Individually, the TESA-blot performed the closest to the gold standard; however, it is not commercially available.

Anemia is a common issue in surgical patients and has been associated with worse clinical outcomes, such as a higher probability of transfusions and longer hospital stay. Therefore, Patient Blood Management programs are actively aiming to achieve early identification and treatment of anemia, previous to the surgery.In this study, preoperative hemoglobin within the Blood Order Schedule (BOS) at 16 blood centers in several Brazilian regions were retrospectively evaluated. Data regarding hemoglobin, age, gender and Brazilian regions were further analyzed.From the 20,201 BOSs evaluated, the mean age was 55.65 ± 23.52 years old, with an overall prevalence of preoperative anemia of 60.9%. Women had a lower mean preoperative hemoglobin (11.74 ± 2.84 for women and 12.27 ± 3.06 for men) and higher prevalence of anemia than men (66% of females and 52.2% of males). The individuals over 65 years old and under 18 were the most affected by preoperative anemia. All regions had a high prevalence of preoperative anemia, without any direct association with the Human Development Index.In summary, upon evaluating the BOS, our study showed a high prevalence of preoperative anemia in all Brazilian regions, regardless of the gender and age group, but that women and individuals less than 18 or over 65 years old have an even higher prevalence of preoperative anemia. This information can identify the institutions in which preoperative anemia is a critical issue and in which new strategies, such as preoperative screening clinics, might be helpful.

Introdução: Descrito pela primeira vez em 1950, o sistema de grupo sanguíneo Duffy é caracterizado por uma glicoproteína (ACKR1) expressa na membrana celular dos eritrócitos, bem como em outros tecidos. Indivíduos que possuem o polimorfismo rs2814778 no gene ACKR1 apresentam um fenótipo Fya e Fyb negativo (Duffy-null), frequentemente relacionado a neutropenia étnica benigna, embora este mecanismo ainda não esteja completamente esclarecido. Por esse motivo, a avaliação deste fenótipo deve fazer parte do roteiro de investigação dos pacientes com neutropenia, sobretudo naqueles em que há suspeita de neutropenia étnica benigna. Objetivos: Correlacionar a fenotipagem por técnica imuno-hematológica dos antígenos Fya e Fyb, a genotipagem para o sistema Duffy e a presença do polimorfismo rs2814778 em pacientes neutropênicos, de modo a definir se apenas a fenotipagem é suficiente para a determinação do fenótipo Duffy-null, em pacientes portadores de neutropenia. Métodos: Trata-se de um estudo transversal incluindo 41 pacientes, 28 adultos e 13 pediátricos atendidos no período de dois anos no Ambulatório de Neutropenias da Disciplina de Hematologia e Hemoterapia da Universidade Federal de São Paulo (UNIFESP). As amostras foram submetidas a fenotipagem dos antígenos Fya e Fyb, genotipagem do gene ACRK1 e a pesquisa do polimorfismo rs2814778. Resultados: Do total de pacientes analisados, 31,70% apresentavam idade < 18 anos (pediátricos) e 68,29% ≥ 18 anos (adultos). Dentre o grupo de pacientes pediátricos, a prevalência do fenótipo Duffy-null foi de 61,53%, enquanto no grupo de pacientes adultos foi de 82,14%. Considerando o total de pacientes, a prevalência do fenótipo foi de 75,60%. Quando comparados os testes imuno-hematológicos e moleculares, 97,46% apresentaram resultados concordantes e apenas um paciente (2,54%) apresentou resultado discrepante, demonstrando alta correlação entre as técnicas (coeficiente κ = 0,935). Considerando estes dados, pode-se observar que a fenotipagem para o sistema Duffy apresentou sensibilidade de 100%, especificidade de 90% e acurácia de 97%. Discussão: A pesquisa do fenótipo Duffy-null é um passo essencial na investigação de pacientes portadores de neutropenia. Embora a fenotipagem do sistema Duffy por métodos imuno-hematológicos seja amplamente disponível na maior parte dos serviços, a genotipagem apresenta custo mais elevado e pode não ser acessível. A alta concordância entre as técnicas analisadas demonstrou segurança na realização apenas dos testes imuno-hematológico para determinação do fenótipo Fya e Fyb, sem que seja necessária a realização de análise genética, rotineiramente, na população neutropênica. Conclusão: A concordância obtida entre os testes realizados foi alta, demonstrando que a fenotipagem do sistema Duffy aparenta ser um teste sensível e acurado para a determinação do fenótipo Duffy-null nos pacientes portadores de neutropenia.

Since December 2019, a newly identified coronavirus disease 2019 (COVID-19) has spread in China and the rest of world. There are many doubts regarding pathogenesis as well complications due to COVID-19. We report a case with association between thrombocytopenia and the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection after exclusion of other possible etiology in a patient with previous controlled idiopathic thrombocytopenic purpura.

Introdução: A anemia hemolítica autoimune (AHAI) tem sido associada a muitas patologias conhecidas, incluindo doenças autoimunes, linfoproliferativos e certas doenças infecciosas, principalmente nos casos por anticorpos a frio. Tem surgido alguns relatos de caso de doença por SARS-Cov2 (COVID-19) associado a AHAI; no entanto, essa potencial associação ainda não é clara. Aqui relatamos uma serie 3 casos de Síndrome de aglutininas a frio (CAS), associada a infecção por Covid-19. Relato de caso: Três pacientes, com idades de 53 a 65 anos, sendo 2 homens e 1 mulher, foram admitidos em nosso serviço de fevereiro a maio de 2021, devido a infecção por Covid-19. Dois apresentavam síndrome aguda de angústia respiratória, mas sem necessidade de ventilação mecânica. Todos apresentavam anemia macrocítica, com hemoglobina que variava de 6,5-9,1 g/dL, DHL aumentado (311-679), e 2 com Birrubina indireta aumentada (1,05-2,55). Todos apresentavam teste de antiglobulina direto fortemente positivo as custas de C3d, com amplitude térmica de 24°C, e título a frio de 64-256. Dois pacientes não apresentavam comorbidades, 1 paciente havia sido internado recentemente para correção cirurgica de Doença arterial Cronica. Dois pacinetes fora tranfundidos com CH, entrtanto nenhum tratamento específico para AHAI foi estabelecido. Uma paciente foi transferida e perdeu seguimento e dois pacientes recuperam totalmente do quadro, e mantém-se após 3 e 4 meses de infecção com Hb >12 g/dL, sem necessidade de tratamento. Discussão e conclusão: Doença resultante de infecção por Covid-19 está associada a várias anormalidades hematológicas, incluindo linfopenia, fênomenos trombo-embólicos, trombocitopenia imune, síndrome antifosfolipídeo. Tem surgido alguns relatos de casos no último ano, associando AHAI a infecção por covid-19 e sugerindo que a desregulação imunológica teria como a etiologia subjacente o SARS-CoV-2. Aqui, detalhamos uma série de 3 paciente com infecção sintomática por SARS-CoV-2 que apresentram anemia sintomática de leve a grave e a a investigação foi consistente com anemia hemolítica autoimune por anticorpos a frio secundária à infecção por covid-19 (CAS), diagnóstico raro em nosso meio.

Introdução: O Brasil apresenta uma população de 213 milhões de habitantes, com uma composição étnica oriunda de indígenas, africanos e europeus. A investigação da distribuição dos alelos dos antígenos de neutrófilos humanos (HNA) em regiões representativas torna-se uma importante ferramenta para se avaliar os riscos de aloimunização em uma população tão miscigenada. Objetivo: Investigar a distribuição dos alelos HNA em doadores de sangue das regiões norte, nordeste e sudeste do Brasil, que apresentam uma ancestralidade indígena, negroide e caucasiana, respectivamente. Casuística e métodos: Trata-se de um estudo transversal, envolvendo amostras de doadores de sangue do norte do país (Pará, 50 amostras); nordeste (Alagoas, 50 amostras); e sudeste (São Paulo, 300 amostras). A genotipagem dos sistemas HNA-1 e HNA-4; HNA-3 e HNA-5 foi realizada através de PCR-SSP e PCR-RFLP respectivamente. Resultados: Entre os sistemas analisados os que apresentaram uma diferença estatística significativa entre as regiões estudadas foram HNA-1 e HNA-5. Os alelos FCGR3B*01 e *02 apresentaram uma distribuição inversa na região norte (0,554 e 0,376) quando comparado com as regiões sudeste e nordeste do país (0,315 e 0,637; e 0,336 e 0,572, respectivamente. p

Background The allogeneic transfusion-related immunomodulation (TRIM) may be responsible for an increase in survival of renal transplants but in contrast it could increase the rate of bacterial infections or the recurrence rate of tumors post-operatively. Objective This review focuses in the implications of perioperative allogeneic transfusions on the immune-inflammatory response of surgical transfused patients. Results ABTs modify immune functions in recipients including decrease of the number of lymphocytes; decrease the CD4 cells; decrease the CD4/CD8 T-cell ratio; decrease NK cells; and decrease the lymphocyte response to mitogens. TRIM effects may be mediated by allogeneic white cells present in blood products; soluble peptides present in transfused plasma; and/or biologic mediators released into the supernatant of blood units. A recent systematic review and meta-analysis including 36 clinical observational studies (n = 174,036) concluded that perioperative ABTs not only decreased overall survival and reduced colorectal cancer-specific survival. Furthermore ABTs increased the rate of infectious, cardiac, pulmonary and anastomotic complications in colorectal cancer patients undergoing surgery. Conclusions It has been demonstrated by laboratory tests that TRIM is associated with transfusion recipient immune alterations but its influence in colorectal cancer recurrence after resection remains controversial though may exist. Surgical techniques reducing intraoperative blood loss have limited the number of ABTs perioperatively, however increase in mortality continues to be reported in literature after ABT in colorectal cancer surgery. Poor survival associated to TRIM in colorectal cancer might be due to higher number of allogeneic transfused units and/or prolonged length of blood storage.

Background Antigens from the Rh and Kell systems are recognized as the most immunogenic in clinical practice. This study evaluated the possible molecular mechanisms involved in the interaction of antigenic peptides with the DRB1 molecules, which help to explain the high frequency of anti-K and association of D + C antibodies in transfusion and incompatible pregnancy. Study design and methods We included 201 patients with antibodies against antigens from the Rh and Kell systems and compare them with 174,015 controls. HLA-DRB1 genotyping and in silico analysis were performed. The NetMHCIIpan software was used to identify RhD-, RhCE-, and KEL-derived anchor peptides that bind to DRB1 molecules. Results HLA-DRB1*15 is associated with an increased risk of D, C, E, and K alloimmunization, while the HLA-DRB1*01 and *12 alleles are overrepresented in patients with anti-C and anti-D, respectively. In silico analysis showed that three polymorphic points (60I, 68S, and 103S) common to C and D antigens can be presented by several DRB1 molecules, including DRB1*15:01. The DRB1*09:01 molecule, although not showing statistical significance, was able to interact strongly with almost all five anchor peptides from the sequence containing the polymorphic determinants of E antigen, except 217-WMFWPSVNS-225. Conclusion The DRB1*15 molecule has specific physicochemical characteristics in residues 11P and 13R in the P4 pocket that can favor the response to various antigenic peptides. Anti-K alloimmunization is unrestricted for interaction with specific DRB1 molecules, which suggests that almost all individuals in our population have DRB1 molecules capable of binding to KEL-derived anchor peptides and produce anti-K when stimulated.

Introduction Autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), and autoimmune neutropenia (AIN) are reported in the literature after liver, intestinal, heart, pancreas, and kidney transplants. We report a case of autoimmune pancytopenia (AIHA, AIN and ITP) 9 years after liver transplantation with confirmed erythrocyte and neutrophil auto-antibodies. Case report A 49 years old man was admitted to our hospital presented with dysentery and fever, with history of liver transplantation in 2008. Laboratory evaluation demonstrated hemoglobin: 7.2 g/dL, granulocytes: 0.10 × 109/L and platelets: 15 × 109/mm³; indirect bilirubin: 3.62 mg/dL; lactate dehydrogenase: 603 U/L. Direct antiglobulin test revealed a monospecific anti-IgG plus C3 and the acid eluate was reactive to all panel red cells, consistent with an AIHA. Granulocyte immunofluorescence test (GIFT) and agglutination test (GAT) were reactive for granulocytes. Test with Luminex technology for human neutrophil antigen (HNA) antibody detection was strong reactive with beads expressing HNA-1a, -1b, -1c, -2, -4a and -5a antigens. HNA genotyping revealed the presence of the corresponding antigens, confirming the autoantibodies. Test with Luminex technology for human leucocyte antigen (HLA) antibody detection was negative. Monoclonal antibody immobilization of platelet antigens (MAIPA) assay was negative. Viral causes were excluded. The condition was compatible with clinical onset of autoimmune pancytopenia. Prednisone was administered at an initial dose of 1 mg/kg/day and immunosuppressive therapy was adjusted. This treatment resulted in rapid resolution of pancytopenia. Conclusion Combined autoimmune pancytopenia (AIHA, AIN and ITP) is a rare condition that may occur after liver transplantation. Early recognition of this phenomenon permits appropriate treatment.

BACKGROUND Neonatal alloimmune neutropenia results from maternal alloimmunization to human neutrophil antigens. The alloantibodies involved in neonatal alloimmune neutropenia are against human neutrophil antigens HNA-1a, HNA-1b, HNA-1c, HNA-1d, HNA-2, HNA-3a, HNA-4a, HNA-4b, and HNA-5a; however, to date, antibodies specific to HNA-3b have not been reported. STUDY DESIGN AND METHODS Blood samples from 10,000 unselected neonates were analyzed, resulting in the selection of 88 neutropenic newborns (neutrophil count

Background and objectives The high homology and the inverted orientation of RHD and RHCE may give rise to non-functional and aberrant RH alleles. RH genotyping is used to screen RH matched donors to African descent patients. This study aimed to define a strategy for testing RHD and RHCE variants in blood donors to provide compatible units for transfusion of patients with haematological diseases. Materials and methods Samples from 132 patients [101 Sickle cell disease (SCD), 14 myelodysplastic syndrome (MDS), 17 acute myelogenous leukaemia (AML)] and 198 Brazilian donors were studied. Major blood group alleles, RHD, RHCE alleles and RHD zygosity were determined by the blood-MLPA assay. Sequencing was performed to determine RHD and RHCE variant subtypes. A match was an RH genotype that did not encode Rh antigens absent in the patient, along with matching for ABO, MNS, KEL, FY, JK and DI antigens. Results Overall, 7·6% of blood donors and 17.4% of patients presented RH genotypes that predict expression of partial Rh antigens or lack of high prevalence Rh antigens. From 23 patients with clinically relevant RH genotypes, 15 had available matched donors. Conclusion We report the presence of clinically relevant RH genotypes in SCD and in non-SCD patients. In our admixed population, many patients carry variant RHCE alleles in heterozygosity with normal RHCE alleles. Thus, our results suggest that donors could be selected based on the normal RH allele.

Background: KELnull (K₀) persons can produce clinically significant anti-KEL5 antibody after transfusion and/or pregnancy, requiring K₀ blood transfusion when indicated. 37 K₀ alleles have been reported in studies over different populations, but none in Amerindian-Caucasian descendants from South America. The aim of this study was to identify the molecular basis of K₀ phenotype in Brazilians. Methods: We investigated three K₀ samples from different Brazilian blood banks (Recife, Manaus, and Vila Velha) in women with anti-KEL5. KEL antigen typing was performed by serologic techniques, and the K₀ status was confirmed by flow cytometry. PCR-RFLP and DNA sequencing of the KEL coding and exon-intron regions were also performed. Results: RBCs of the 3 patients were phenotyped as KEL:-1,-2,-3,-4,-7. The 3 patients had the same KEL*02/02 genotype and were negative for KEL*02.03 and KEL*02.06 alleles. The Recife K₀ patient was homozygous for IVS16 + 1g>a mutation (KEL*02N.31 allele). The flow cytometry with anti-KEL1, anti-KEL2, anti-KEL3, anti-KEL4, and anti-CD238 confirmed the K₀ phenotype. In addition, we found the c.1042C>T mutation (KEL*02N.04 allele) in both the Manaus K₀ and the Vila Velha K₀ patients. Conclusion: This report represents the first study of K₀ molecular basis performed in Amerindian-Caucasian descendants from South America.

Background and Objectives Transfusion-related acute lung injury (TRALI) is characterized by leukocyte transmigration and alveolar capillary leakage shortly after transfusion. TRALI pathogenesis has not been fully elucidated. In some cases, the infusion of alloantibodies (immune model), whereas in others the combination of neutrophil priming by proinflammatory molecules with the subsequent infusion of biological response modifiers (BRMs) in the hemocomponent (non-immune model) have been implicated. Our aim was to compare the pathological events involved in TRALI induced by antibodies or BRMs using murine models. Materials and Methods In the immune model, human HNA-2+ neutrophils were incubated in vitro with a monoclonal antibody (anti-CD177, clone 7D8) directed against the HNA-2 antigen and injected i.v. in NOD/SCID mice. In the non-immune model, BALB/c mice were treated with low doses of lipopolysaccharide (LPS) followed by platelet-activating factor (PAF) infusion 2 h later. Forty minutes after PAF administration, or 6 h after neutrophil injection, lungs were isolated and histological analysis, determination of a variety of cytokines and chemokines including keratinocyte-derived chemokine (KC), MIP-2, the interleukins IL-1β, IL-6, IL-8 as well as TNFα, cell influx and alveolar capillary leakage were performed. Results In both models, characteristic histological findings of TRALI and an increase in KC and MIP-2 levels were detected. In contrast to the immune model, in the non-immune model, there was a dramatic increase in IL-1β and TNFα. However, capillary leakage was only detected if PAF was administrated. Conclusions Regardless of the triggering event(s), KC, MIP-2 and integrins participate in TRALI pathogenesis, whereas PAF is essential for capillary leakage when two events are involved.

Summary Introduction: Autoimmune haemolytic anaemia (AIHA) is defined as the increased destruction of red blood cells (RBCs) in the presence of anti-RBC autoantibodies and/or complement. Its pathogenesis is multifactorial and includes changes in mechanisms of cytokine production and functionality. A number of recent studies have implicated cytokines polymorphisms in the pathogenesis of autoimmune diseases. The aim of this study was to determine the frequency of polymorphisms of tumour necrosis factor alpha (TNF-α), lymphotoxin-α (LT-α), interleukin 10 (IL-10), interleukin 12 (IL-12) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) in patients with AIHA in comparison with healthy individuals. Methods: The study population consisted of 17 patients with AIHA and 40 healthy controls. The polymorphisms for TNF-α−308, LT-α +252, IL-10 −592, IL-12 +1188 and CTLA-4 +49 were examined by polymerase chain reaction followed by specific restriction enzyme digestion. Results: There was no significant difference in the phenotypic distributions of polymorphisms of the TNF-α, IL-10, IL-12 and CTLA-4 between the patients and controls. Compared with healthy controls, patients with AIHA had a significant higher frequency of LT-α (+252) AG phenotype (41%vs. 13%; P = 0.032). Conclusion: In this study, no significant differences on the frequency of TNF-α, IL-10, IL-12 and CTLA-4 polymorphisms between patients with AIHA and controls was found, suggesting that the targeted polymorphisms do not influence on the emergence and evolution of the disease. However, the LT-α +252 polymorphism might have an effect for AIHAI development, suggesting that further studies are necessary to clear up this question.