Acute exacerbation of immunoglobulin A nephropathy complicated by alveolar hemorrhage after coronavirus disease 2019 vaccination: A case report.

RATIONALE: Reports have suggested a relationship between coronavirus disease 2019 (COVID-19) vaccination and new-onset or recurring renal diseases, of which immunoglobulin A (IgA) nephropathy is a representative disease. Alveolar hemorrhage in patients with IgA nephropathy is rare but reportedly has a high mortality and morbidity. To our knowledge, there have been no reports regarding the development of IgA nephropathy with alveolar hemorrhage following COVID-19 vaccination. PATIENTS CONCERN: A 23-year-old Japanese man presented with hemoptysis and peripheral edema a few days after receiving a second dose of a COVID-19 mRNA vaccine. Severe renal failure and alveolar hemorrhage were noted thereafter, and renal biopsy showed crescentic glomerulonephritis with mesangial proliferation accompanied by mesangial electron-dense deposits containing IgA. Renal biopsy tissue also showed chronic histological changes suggestive of acute exacerbation of preexisting IgA nephropathy. DIAGNOSIS: The diagnosis of IgA nephropathy complicated by alveolar hemorrhage was made. INTERVENTIONS AND OUTCOMES: Renal function did not recover despite treatment with high-dose steroids; the patient was maintained on hemodialysis and eventually underwent successful renal transplantation. LESSONS: The present case suggested that although extremely rare, severe renal failure requiring renal replacement therapy could occur in patients with IgA nephropathy after COVID-19 vaccination. Future accumulation of similar cases is needed to predict the risk of renal injury following vaccination.

Changes in intestinal homeostasis and immunity in a cigarette smoke- and LPS-induced murine model for COPD: the lung-gut axis.

Chronic obstructive pulmonary disease (COPD) is often associated with intestinal comorbidities. In this study, changes in intestinal homeostasis and immunity in a cigarette smoke (CS)- and lipopolysaccharide (LPS)-induced COPD model were investigated. Mice were exposed to cigarette smoke or air for 72 days, except days 42, 52, and 62 on which the mice were treated with saline or LPS via intratracheal instillation. Cigarette smoke exposure increased the airway inflammatory cell numbers, mucus production, and different inflammatory mediators, including C-reactive protein (CRP) and keratinocyte-derived chemokine (KC), in bronchoalveolar lavage (BAL) fluid and serum. LPS did not further impact airway inflammatory cell numbers or mucus production but decreased inflammatory mediator levels in BAL fluid. T helper (Th) 1 cells were enhanced in the spleen after cigarette smoke exposure; however, in combination with LPS, cigarette exposure caused an increase in Th1 and Th2 cells. Histomorphological changes were observed in the proximal small intestine after cigarette smoke exposure, and addition of LPS had no effect. Cigarette smoke activated the intestinal immune network for IgA production in the distal small intestine that was associated with increased fecal sIgA levels and enlargement of Peyer's patches. Cigarette smoke plus LPS decreased fecal sIgA levels and the size of Peyer's patches. In conclusion, cigarette smoke with or without LPS affects intestinal health as observed by changes in intestinal histomorphology and immune network for IgA production. Elevated systemic mediators might play a role in the lung-gut cross talk. These findings contribute to a better understanding of intestinal disorders related to COPD.

Therapeutic immunoglobulin A antibody for dysbiosis-related diseases.

Dysbiosis is alterations in the microbial composition compared with a healthy microbiota and often features a reduction in gut microbial diversity and a change in microbial taxa. Dysbiosis, especially in the gut, has also been proposed to play a crucial role in the pathogenesis of a wide variety of diseases, including inflammatory bowel disease, colorectal cancer, cardiovascular disease, obesity, diabetes and multiple sclerosis. A body of evidence has shown that intestinal polymeric immunoglobulin A (IgA) antibodies are important to regulate the gut microbiota as well as to exclude pathogenic bacteria or viral infection such as influenza and SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) at mucosal sites. Since the 1970s, trials for oral administration of therapeutic IgA or IgG have been performed mainly to treat infectious enteritis caused by pathogenic Escherichia coli or Clostridium difficile. However, few of them have been successfully developed for clinical application up to now. In addition to the protective function against intestinal pathogens, IgA is well known to modulate the gut commensal microbiota leading to symbiosis. Nevertheless, the development of therapeutic IgA drugs to treat dysbiosis is not progressing. In this review, the advantages of therapeutic IgA antibodies and the problems for their development will be discussed.

Características de algunos parámetros de la inmunidad humoral y celular en pacientes con linfedema / Characteristics of some humoral and cellular immunity´s parameters in patients with lymphedema

Introducción: El linfedema es una enfermedad crónica con un impacto negativo sobre la salud de las personas que lo padecen. Este se considera un problema de salud subestimado y subregistrado, por lo que requiere de mayores esfuerzos investigativos y sanitarios. Objetivo: Identificar las características de algunos parámetros de la inmunidad humoral y celular en pacientes con linfedema del municipio El Cerro. Métodos: Se realizó un estudio descriptivo en 48 pacientes residentes en el municipio Cerro, atendidos en consulta externa del Instituto Nacional de Angiología y Cirugía Vascular en el período 2011-2015. El grupo se dividió en 24 pacientes con linfedema y 24 sin la enfermedad. A todos se les cuantificaron las concentraciones de las inmunoglobulinas (A, G y M) y de la proteína C reactiva. También se les hizo la prueba de hipersensibilidad retardada. Se utilizó chi cuadrado no paramétrico para asociar el estado inmunológico con la presencia de linfedema, la etiología y los estadios de este. Se trabajó con una confiabilidad del 95 por ciento (p < 0,05). Resultados: Predominaron los pacientes del sexo femenino (58,3 por ciento) y los de 60 años y más (29,2 por ciento). Hubo mayor frecuencia de linfangitis recurrentes (70,8 por ciento), con predominio del linfedema secundario en estadio IIb (45,8 por ciento); de afectación del miembro inferior derecho (45,8 por ciento), con una diferencia significativa de las inmunoglobulinas (IgA e IgG); y de frecuencia de pacientes anérgicos (91,7 por ciento), con proteína C reactiva positiva (45,8 por ciento). Conclusiones: Los pacientes con linfedema tienen afectados su sistema inmune, con mayor frecuencia de anérgicos, diminución de las inmunoglobulinas IgA e IgG, y positividad de proteína C reactiva(AU)

Introduction: Lymphedema is a chronic disease with a negative impact on the health of patients with lymphedema. It is considered an underestimated and sub-recorded health problem, which requires greater research and health efforts. Objective: Identify the characteristics of some parameters of humoral and cellular immunity in patients with lymphedema from Cerro municipality. Methods: A descriptive study was carried out in 48 patients living in Cerro municipality, who were attended in the external consultation of the National Institute of Angiology and Vascular Surgery in the period 2011-2015. The group was divided into 24 patients with lymphedema and 24 patients without the disease. The concentrations of immunoglobulins (A, G and M) and C-reactive protein were quantified in all of them. The test of delayed hypersensitivity was also perfomed. Non-parametric chi-square was used to associate immune state with the presence of lymphedema, etiology and lymphedema stages. Reliability was of 95 percent (p<0.05). Results: Female patients predominated (58.3 percent) and those of 60 years and older (29.2 percent). There was a higher frequency of recurrent lymphangitis (70.8 percent), predominantly stage II b secondary lymphedema (45.8 percent); lower right limb involvement (45.8 percent), with a significant difference of immunoglobulins (IgA and IgG); and frequency of anergic patients (91.7 percent), with positive C-reactive protein (45.8 percent). Conclusions: Patients with lymphedema have their immune system affected, more frequently the anergic ones, a decrease of IgA and IgG immunoglobulins, and positivity of C-reactive protein(AU)

When Therapeutic IgA Antibodies Might Come of Age.

BACKGROUND: Extensive efforts have been made in optimizing monoclonal immunoglobulin (Ig)G antibodies for use in clinical practice. Accumulating evidence suggests that IgA or anti-FcαRI could also represent an exciting avenue toward novel therapeutic strategies. SUMMARY: Here, we underline that IgA is more effective in recruiting neutrophils for tumor cell killing and is potently active against several pathogens, including rotavirus, poliovirus, influenza virus, and SARS-CoV-2. IgA could also be used to modulate excessive immune responses in inflammatory diseases. Furthermore, secretory IgA is emerging as a major regulator of gut microbiota, which impacts intestinal homeostasis and global health as well. As such, IgA could be used to promote a healthy microbiota in a therapeutic setting. Key messages: IgA combines multifaceted functions that can be desirable for immunotherapy.

Adult-onset IgA vasculitis (Henoch-Schönlein): Update on therapy.

Immunoglobulin A vasculitis (IgAV, formerly Henoch-Schönlein purpura) is a systemic inflammatory disease affecting small vessels. While it is common and usually benign in childhood, in adults it is rarer has a more severe course. Its main manifestations are cutaneous purpura, arthralgias or arthritis, acute enteritis and glomerulonephritis. Renal involvement is associated with a poor prognosis in adults. The treatment of adult-onset IgAV is still a matter of debate: although in patients with a non-severe phenotype remission can occur spontaneously, more severe cases may need immunosuppressive therapy. There are some areas of uncertainty with respect to the efficacy of immunosuppressive regimens: almost all data come from studies performed in children or from patients with IgA nephropathy and/or IgA-crescentic glomerulonephritis. The only randomised study performed in adults with IgAV and renal involvement showed that immunosuppressive therapy with cyclophosphamide did not improve renal outcome nor did it affect patient survival. The possible efficacy of other drugs is reported only in small case series. Recent evidences show that rituximab could be an effective therapeutic option for adult-onset IgAV, but this also needs to be confirmed in controlled trials. In this review, we focus on therapeutic options for adult-onset IgAV treatment, and discuss the main results of the studies performed so far.

[IgA vasculitis secondary to Klebsiella pneumoniae infection]. / Vascularite à IgA satellite d'une pneumopathie abcédée à Klebsiella pneumoniae.

INTRODUCTION: IgA vasculitis is a leucocytoclastic vasculitis of small vessels with immune deposits of IgA. It tends to occur in a post-infectious context, though the pathogenic agent is rarely found. OBSERVATION: We report, for the first time, the case of an 81-year old patient who presented with an acute IgA vasculitis with cutaneous and joint involvement during a Klebsiella pneumoniae respiratory infection. Remission of vasculitis was observed after antibiotic therapy alone. CONCLUSION: This observation reminds us of the need to search carefully for any pathogenic agent that may be driving IgA vasculitis as this may be important both for understanding aetiology and for treatment.

IgA-mediated autoimmune hemolytic anemia in an infant.

Autoimmune Hemolytic anemia (AIHA) a relatively uncommon form of hemolytic anemia in children, occurs due to the premature destruction of red blood cells caused by presence of autoantibodies directed against antigens on RBCs. Warm reactive AIHA is the most common form due to IgG isotype of immunoglobulin class binding to autologous RBCs at 370C and confirmed with a positive DAT screening. We present a case of DAT-negative primary warm AIHA in an infant due to IgA antibody. A 10 month old male infant presented with dark colored urine and irritability for past two months, with associated history of fever, diarrhea and vomiting. He had received one red cell transfusion 10 days prior. On physical examination he had pallor with tachycardia without splenomegaly. On investigation his hemoglobin was 5.8 g/dl, WBC 25.9 × 103/mm3 and normal platelets counts. Peripheral blood smear had spherocytes and biochemical values showed high bilirubin and LDH. Immunohematological work up revelaed polyspecific DAT was negative but monospecific DAT screening showed strong (4+) positivity for IgA and a weak IgG positivity. The patient was diagnosed as IgA-mediated Warm AIHA and was started on prednisolone at 2 mg/kg/day following which hemoglobin improved over the next 2 months. After 2 weeks, prednisolone was tapered and stopped by the end of 3 months. Patients with clinical and laboratory evidence of acute hemolysis, an additional screening for IgA antibody may be done even in cases where poly-specific DAT is negative. Early detection helps in avoiding further investigations and provide efficient management.

Personalized medicine with IgGAM compared with standard of care for treatment of peritonitis after infectious source control (the PEPPER trial): study protocol for a randomized controlled trial.

BACKGROUND: Peritonitis is responsible for thousands of deaths annually in Germany alone. Even source control (SC) and antibiotic treatment often fail to prevent severe sepsis or septic shock, and this situation has hardly improved in the past two decades. Most experimental immunomodulatory therapeutics for sepsis have been aimed at blocking or dampening a specific pro-inflammatory immunological mediator. However, the patient collective is large and heterogeneous. There are therefore grounds for investigating the possibility of developing personalized therapies by classifying patients into groups according to biomarkers. This study aims to combine an assessment of the efficacy of treatment with a preparation of human immunoglobulins G, A, and M (IgGAM) with individual status of various biomarkers (immunoglobulin level, procalcitonin, interleukin 6, antigen D-related human leucocyte antigen (HLA-DR), transcription factor NF-κB1, adrenomedullin, and pathogen spectrum). METHODS/DESIGN: A total of 200 patients with sepsis or septic shock will receive standard-of-care treatment (SoC). Of these, 133 patients (selected by 1:2 randomization) will in addition receive infusions of IgGAM for 5 days. All patients will be followed for approximately 90 days and assessed by the multiple-organ failure (MOF) score, by the EQ QLQ 5D quality-of-life scale, and by measurement of vital signs, biomarkers (as above), and survival. DISCUSSION: This study is intended to provide further information on the efficacy and safety of treatment with IgGAM and to offer the possibility of correlating these with the biomarkers to be studied. Specifically, it will test (at a descriptive level) the hypothesis that patients receiving IgGAM who have higher inflammation status (IL-6) and poorer immune status (low HLA-DR, low immunoglobulin levels) have a better outcome than patients who do not receive IgGAM. It is expected to provide information that will help to close the knowledge gap concerning the association between the effect of IgGAM and the presence of various biomarkers, thus possibly opening the way to a personalized medicine. TRIAL REGISTRATION: EudraCT, 2016-001788-34; ClinicalTrials.gov, NCT03334006 . Registered on 17 Nov 2017. Trial sponsor: RWTH Aachen University, represented by the Center for Translational & Clinical Research Aachen (contact Dr. S. Isfort).

Diffuse Alveolar Hemorrhage in IgA Vasculitis with an Atypical Presentation.

IgA vasculitis (IgAV) commonly occurs in young children, who present with a tetrad of purpura, abdominal pain, arthralgia and nephritis. Diffuse alveolar hemorrhage (DAH) is a rare complication of IgAV. We herein report an adult case of IgAV with a presentation of DAH and nephritis (pulmonary renal syndrome, PRS), but without other typical manifestations, such as purpura, abdominal pain and arthralgia. A 33-year-old man presented with hemoptysis and a low-grade fever and was diagnosed to have IgAV based on the results of a renal biopsy. Treatment with corticosteroids, cyclophosphamide, and plasmapheresis was effective. IgAV should therefore be considered in the differential diagnosis of adult PRS.

Success of anti-CD20 monoclonal antibody treatment for severe autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, and immunoglobulin M autoantibodies in a child: a case report.

BACKGROUND: Autoimmune hemolytic anemia is rare in children. First-line therapies for this disease consist of corticosteroids and intravenously administered immunoglobulin that are effective in most patients. However, a small proportion of cases (5 to 10%) is refractory to these therapies and may represent a medical emergency, especially when hemolysis is due to warm immunoglobulin M. Recently, reports of the use of rituximab in adult autoimmune diseases have shown promising results. In children, there are few studies on the use of rituximab in the treatment for autoimmune hemolytic anemia, especially on its long-term efficacy and adverse effects. CASE PRESENTATION: Here, we report the case of a 10-year-old Tunisian girl with refractory acute autoimmune hemolytic anemia caused by warm-reactive immunoglobulin A, immunoglobulin G, immunoglobulin M, and C3d autoantibodies. First-line treatments using corticosteroids and intravenously administered immunoglobulin were ineffective in controlling her severe disease. On the other hand, she was successfully treated with rituximab. In fact, her hemolytic anemia improved rapidly and no adverse effects were observed. CONCLUSIONS: The case that we report in this paper shows that rituximab could be an alternative therapeutic option in severe acute autoimmune hemolytic anemia with profound hemolysis refractory to conventional treatment. Moreover, it may preclude the use of plasmapheresis in such an urgent situation with a sustained remission.

Pentoxifylline and Pentaglobin adjuvant therapies for neonatal nosocomial sepsis in neonates less than 1500g weight.

OBJECTIVE: To compare different support therapies in very low birth-weight preterm neonates with nosocomial sepsis. METHODS: This clinical pilot study was conducted at the Bagcilar Research and Training Hospital, Istanbul, Turkey, from September 2015 to November 2016. Preterm infants appropriately sized for a gestational age of < 32 weeks and < 1,500g were included in the study. Pentaglobin was initiated on the day of diagnosis of nosocomial sepsis to very low birth-weight preterm neonates as a support therapy in addition to antibiotics: 5 ml/kg per day of pentaglobin was infused over a four-hour period on three consecutive days. Pentoxifylline (5 mg/kg every 6 hours) was administered to premature infants with sepsis on three successive days. RESULTS: Of the 41 neonates, 19(46.3%) were girls and 22(53.7%) were boys. Vital signs, haematologic tables, peripheral blood smear left shift ratio, and blood-gas parameters did not differ significantly between the groups (p>0.05), but the C-reactive protein (mg/dl) values significantly decreased after pentoxifylline treatment (p<0.05). Coagulase-negative staphylococci were the most frequently isolated bacteria in the two groups (n=4; 19% vs. n=4; 20%). There was no difference in isolated microorganisms. There was no significant difference in intraventricular haemorrhage, necrotising enterocolitis, periventricular leukomalacia or symptomatic patent ductus arteriosus in the neonates when comparing the two groups and no systemic reactions were observed during adjuvant therapy in the preterm neonates (p>0.05). The total duration of hospitalisation was 49.46±13.52 days for the pentaglobin group and 44.21±11.1 days for the pentoxifylline group neonates. CONCLUSIONS: Pentoxifylline treatment for nosocomial sepsis decreased C-reactive protein levels and heart rate more than pentaglobin therapy.

[Acute pancreatitis as the presenting feature of an IgA vasculitis: An unusual presentation]. / Pancréatite aiguë inaugurale d'une vascularite à IgA de l'adulte : une manifestation inhabituelle.

INTRODUCTION: IgA vasculitis is a systemic small vessel leukocytoclastic vasculitis characterized by skin purpura, arthritis, abdominal pain and nephritis. Most of the abdominal complications are due to edema and hemorrhage in the small bowel wall, but rarely to acute secondary pancreatitis. CASE REPORT: Here, we report a 53-year-old woman who presented with acute pancreatitis and, secondarily, developed skin purpura and arthritis at the seventh day of the clinical onset. Biological tests and computed tomographic scan allowed to rule out another cause of pancreatitis and IgA vasculitis was diagnosed as its etiology. The outcome was favorable without any relapse on glucocorticoids. CONCLUSION: Despite its rarity, pancreatitis is a potential life-threatening complication of IgA vasculitis in which the role of glucocorticoids and immunosuppressive drugs remains uncertain. A prompt elimination of other usual pancreatitis etiologies is mandatory to improve the management of the patients.

Evaluation of unintended effects in the composition of tomatoes expressing a human immunoglobulin A against rotavirus.

The production of neutralizing immunoglobulin A (IgA) in edible fruits as a means of oral passive immunization is a promising strategy for the inexpensive treatment of mucosal diseases. This approach is based on the assumption that the edible status remains unaltered in the immunoglobulin-expressing fruit, and therefore extensive purification is not required for mucosal delivery. However, unintended effects associated with IgA expression such as toxic secondary metabolites and protein allergens cannot be dismissed a priori and need to be investigated. This paper describes a collection of independent transgenic tomato lines expressing a neutralizing human IgA against rotavirus, a mucosal pathogen producing severe diarrhea episodes. This collection was used to evaluate possible unintended effects associated with recombinant IgA expression. A comparative analysis of protein and secondary metabolite profiles using wild type lines and other commercial varieties failed to find unsafe features significantly associated with IgA expression. Preliminary, the data indicate that formulations derived from IgA tomatoes are as safe for consumption as equivalent formulations derived from wild type tomatoes.

[Anti-HIV antibodies: multiple antiviral activities]. / Les anticorps anti-VIH - de multiples activités antivirales.

Sexual transmission is currently the major route of HIV infection worldwide. Neutralizing antibodies (IgG) have demonstrated their role in the protection from experimental challenge in non-human primate's model. However, these types of antibodies display very specific characteristics and are extremely difficult to induce. Interestingly, antibodies devoid of neutralizing activity have demonstrated additional inhibitory mechanisms dependant of their binding to Fc receptors expressed on antigen presenting cells. These cells may play decisive role at early sexual transmission as they have been proposed to be the first HIV target at the mucosal site. Data from in vivo studies and recent findings following clinical assays demonstrated the importance of these Fc-mediated antibodies dependant mechanism in protection against HIV. Therefore new vaccination strategies including the induction of such type of activities, in addition to neutralizing antibodies, should be developed.

Dermatosis ampollosa inducida por inmunoglobulina A lineal con clínica de síndrome DRESS por sulfasalazina / Sulfasalazine-Induced Linear Immunoglobulin A Bullous Dermatosis with DRESS

La dermatosis inducida por inmunoglobulina A (IgA) lineal es una enfermedad ampollosa mediada inmunológicamente que se define por presentar un depósito lineal de IgA a lo largo de la membrana basal. Habitualmente es idiopática y ocasionalmente se asocia con algunos fármacos. Describimos el caso de una mujer de 60 años con artritis reumatoide en tratamiento con sulfasalazina, que desarrolló un cuadro de dermatosis IgA lineal con clínica de drug-rash with eosinophilia and systemic symptoms (DRESS) el cual respondió al suspender el fármaco causal más tratamiento con corticoides sistémicos durante 2 meses. Este es el primer caso descrito de dermatosis IgA lineal con clínica de DRESS relacionado con la sulfasalazina. Creemos que es importante tener en cuenta esta asociación para poder incluir la sulfasalazina en el listado de fármacos que pueden producir dermatosis IgA lineal por fármacos (AU)

Linear immunoglobulin (Ig) A dermatosis is an immune-mediated bullous disease characterized by linear deposits of IgA along the basal membrane. While usually idiopathic, it can occasionally be induced by drug exposure. We report the case of a 60-year-old woman with rheumatoid arthritis being treated with sulfasalazine who developed linear IgA dermatosis and drug rash with eosinophilia and systemic symptoms (DRESS). The dermatosis and associated symptoms resolved following withdrawal of the drug and treatment with systemic corticosteroids for 2 months. This is the first report of sulfasalazine-induced linear IgA dermatosis in association with DRESS and we believe that sulfasalazine should be added to the list of drugs that can cause linear IgA dermatosis (AU)

Adverse effects of IgG therapy.

IgG is widely used for patients with immune deficiencies and in a broad range of autoimmune and inflammatory disorders. Up to 40% of intravenous infusions of IgG may be associated with adverse effects (AEs), which are mostly uncomfortable or unpleasant but often are not serious. The most common infusion-related AE is headache. More serious reactions, including true anaphylaxis and anaphylactoid reactions, occur less frequently. Most reactions are related to the rate of infusion and can be prevented or treated just by slowing the infusion rate. Medications such as nonsteroidal anti-inflammatory drugs, antihistamines, or corticosteroids also may be helpful in preventing or treating these common AEs. IgA deficiency with the potential of IgG or IgE antibodies against IgA increases the risk of some AEs but should not be viewed as a contraindication if IgG therapy is needed. Potentially serious AEs include renal dysfunction and/or failure, thromboembolic events, and acute hemolysis. These events usually are multifactorial, related to combinations of constituents in the IgG product as well as risk factors for the recipient. Awareness of these factors should allow minimization of the risks and consequences of these AEs. Subcutaneous IgG is absorbed more slowly into the circulation and has a lower incidence of AEs, but awareness and diligence are necessary whenever IgG is administered.

Benefits and risks of IgA in immunoglobulin preparations.

The case of Immunoglobulin A (IgA) in transfusion medicine is unsettled: on one hand IgA is an important component of adaptive immunity and its deficiency may cause disease, on the other its presence in blood products might induce, in rare instances, allergy-like symptoms if not anaphylaxis. The practice with i.v. immunoglobulins currently changes as up to 10% concentrated preparations are given at fast rates hence even trace amounts of IgA contained in these IgG preparations can cause unexpected (side-) effects. Fortunately, the spectrum of sensitive IgA assays, along with anti-IgA screening assays now permits laboratories to narrow down IgA-dependent transfusion reactions to the real cases, in which IgA was the decisive trigger of anaphylaxis, proven or not by the presence of anti-IgA of the IgG or even IgE class. Tolerance to allogenic IgA has recently been reported. The known association of HLA with IgA deficiency (IgAD) has now been completed with an association to the nonsynonymous variant in IFHI1, allowing physicians to more precisely spot recipients at risk for an IgA-dependent transfusion reaction. Our review, along with our own experience here in Switzerland, allows us to conclude that IgA is a beneficial antibody rather than an allergen to be placed at the end of the list of non-infectious transfusion complications such as TRALI, febrile non-hemolytic reactions, purpura or volume overload.