Hypocomplementemia Research Articles

Assessment of C3 and C4 component of complement system in aborted women infected with Toxoplasma gondii

Background: The complement system consists of more than 30 proteins that are either present as soluble proteins in the blood or present as membrane-associated proteins. Inappropriate complement activation and complement deficiencies are the underlying cause of the pathophysiology of many diseases.Methods: A case-control study was conducted to asses role of complement system during toxoplasmosis in Najaf province. Thirty five sera of infected women with toxoplasmosis by investigation antibody against toxoplasmosis for IgG and IgM by ELISA technique were tested to determine the levels of C3 and C4 by using single radial immunodiffusion technique and compared with the ten of control sera of non infected subjects and non-aborted.Results: The high C3 in significant differences(P<0.05) and C4 with no significant differences(P>0.05) levels were found in aborted toxo-positive women in compared with control. Likewise, it was found that association between concentration of C3,C4 and number of abortion.Conclusion: complement were play role in immune response of pregnant women especially against toxoplasmosis that cause abortion to these women.

From clinical observations and molecular dissection to novel therapeutic strategies for primary immunodeficiency disorders.

The field of primary immunodeficiency diseases (PID) is rapidly expanding with more than 300 genetically defined disorders that have been clinically described and molecularly analyzed. The molecular dissection of these entities has led to the discovery of new immunologic pathways and to novel and effective disease-specific therapies. This review provides a summary of these primary immune defects categorized by clinical phenotype and molecular similarity as defined by the International Union of Immunologic Societies (IUIS) Expert Committee for PID. In this synopsis, we discuss the molecular basis of various categories of PIDs including, but not limited to, severe combined immunodeficiencies, primary antibody deficiencies, immune dysregulation syndromes, as well as defects of the innate immune system such as phagocytic abnormalities, autoinflammatory fever syndromes, and complement deficiencies. We have attempted to focus on current strategies to prevent complications, ameliorate symptoms, or cure these disorders by promptly using antimicrobial therapies, immunoglobulin replacement, and hematopoietic stem cell transplantation. In addition, we will explore novel therapies such as molecularly targeted immunosuppression with monoclonal antibodies and specific immunomodulatory agents. Finally, we address experimental therapies targeting specific molecular defects, including gene therapy and gene editing.

Recommendations for the use of meningococcal vaccines in South Africa

Background: Although meningococcal disease (MD) incidence in South Africa is low, Neisseria meningitidis (NM) causes severe disease that is often life-threatening and can cause long-term disabilities. A quadrivalent protein-conjugated meningococcal vaccine (MCV4) is available, and provides protection against 75% of disease causing serogroups in South Africa.Recommendations: We advise vaccination of persons at high risk of meningococcal disease including those with complement deficiency and asplenia; laboratory personnel from reference laboratories who work with NM; and travellers to Saudi Arabia.The need for routine vaccine against meningococcal disease in South Africa is controversial given the current burden of disease. However, due to the high morbidity/mortality of MD we recommend that clinicians consider vaccination of healthy infants and children; HIV-infected persons with a CD4 count > 25%; students attending college /university /military academies; and miners.Conclusion: Protein-conjugated meningo...

Newborn Screening for Primary Immunodeficiency Diseases: The Past, the Present and the Future

Primary immunodeficiency diseases (PID) are a heterogeneous group of disorders caused by inborn errors of immunity, with affected children presenting with severe, recurrent or unusual infections. Over 300 distinct genetic molecular abnormalities resulting in PID have been identified, and this number continues to rise. Newborn screening for PID has been established in many countries, with the majority of centers using a PCR-based T cell receptor excision circle (TREC) assay to screen for severe combined immunodeficiency (SCID) and other forms of T cell lymphopenia. Multiplexed screening including quantitation of kappa-recombining exclusion circles (KREC) has also been described, offering advantages over TREC screening alone. Screening technologies are also expanding to include protein-based assays to identify complement deficiencies and granulocyte disorders. Given the rapid advances in genomic medicine, a potential future direction is the application of next-generation sequencing (NGS) technologies to screen infants for a panel of genetic mutations, which would enable identification of a wide range of diseases. However, several ethical and economic issues must be considered before moving towards this screening strategy.

Genomics of Systemic Lupus Erythematosus: Insights Gained by Studying Monogenic Young-Onset Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a systemic, autoimmune, multisystem disease with a heterogeneous clinical phenotype. Genome-wide association studies have identified multiple susceptibility loci, but these explain a fraction of the estimated heritability. This is partly because within the broad spectrum of SLE are monogenic diseases that tend to cluster in patients with young age of onset, and in families. This article highlights insights into the pathogenesis of SLE provided by these monogenic diseases. It examines genetic causes of complement deficiency, abnormal interferon production, and abnormalities of tolerance, resulting in monogenic SLE with overlapping clinical features, autoantibodies, and shared inflammatory pathways.

Dendritic cells and interferons in systemic lupus erythematosus

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disorder with a genetic basis, and is characterized by the appearance of autoantibodies, the formation and deposition of circulating immune complexes, and chronic inflammation in various organs. It is of multifactorial origin, and in genetically predisposed individuals, environmental factors and hormonal components play a key role in the immune system of the disease. About 25 genetic loci have been identified, indicating the importance in this pathology. However, the concordance rate for SLE is only 25% among monozygotic twins. An example of this is the deficiencies of the initial components in the classical serum complement pathway such as C1q, C2 or C4, which, although rare, confer genetic susceptibility for SLE at a rate of 30% in the case of C4 deficiency, and more than 90% for C1q deficiency. It was also demonstrated that C1q inhibits plasmacytoid dendritic cells (pDCs) in the secretion of interferon-alpha (IFN-α), thus providing a new link between complement deficiency and activation of the IFN pathway. Therefore, IFN-α is considered to have a central role in the pathogenesis of SLE, with high serum concentrations being found in outbreaks of this disease. These IFN exert prominent immunoregulatory effects, suggesting that this cytokine is key, not only in the innate immune system, but also in adaptive immune responses. Taking these facts into account, it can be anticipated that pDCs, the main source of IFN secretion, are involved in this autoimmune disease. In this review, we will focus on the participation of and IFNs in SLE.

Risk factors of disease progression and adverse pregnancy outcome in patients with systemic lupus erythematosus during pregnancy

Objective To investigate the risk factors of disease progression and adverse pregnancy outcome in patients with systemic lupus erythematosus (SLE) during pregnancy. Methods Clinical data of 118 pregnant women with SLE admitted from June 2004 to October 2015 were retrospectively analyzed. The patients were divided into selective pregnant group (group A, n=72 cases) and non-selective pregnant group (group B, n=46) according to the disease activity of SLE. The disease progression and pregnancy outcomes were compared between two groups. Results The various system damages occurred in group B, including hematological damage in 16 cases, kidney damage in 19 cases, erythra in 10 cases, arthritis in 10 and serositis in 12 cases; while the corresponding cases in group A were 10, 14, 6, 4 and 4( χ2=7.133, P= 0.008; χ2=6.658, P=0.010; χ2=4.304, P=0.038; χ2=7.030, P=0.008; χ2=10.095, P=0.001). SLE exacerbation occurred in 28 cases (74%) of group B and 12 cases (17%) of group A (χ2=34.944, P= 0.000). The logistic regression analysis showed that hypocomplementemia, proteinuria, SLEDAI score before pregnancy and positive anti-dsDNA antibody were the risk factors of SLE disease exacerbation during pregnancy. The maternal complications occurred in group B, including pregnancy-induced hypertension in 7 cases, preeclampsia in 10 cases and infections in 11 cases/times; while the corresponding cases (case/time) in group A were 2, 6 and 4 (χ2=4.526, P= 0.033; χ2=4.304, P=0.038; χ2=8.525, P=0.004). There were 14 cases of therapeutic induced labor, 7 case of stillbirth and 27 cases of total fetal loss in group B, while the corresponding cases in group A were 2, 0 and 4 (χ2=18.317, P= 0.000; χ2=9.080, P= 0.003; χ2=40.920, P= 0.000). The logistic regression analysis showed that positive anticardiolipin antibody, proteinuria, SLEDAI score before pregnancy and renal dysfunction during pregnancy were risk factors of fetal loss. There were 87 cases of successful delivery (73.7%), the successful delivery rates were 41.3% (19/46) in group B and 94.4% (68/72) from group A, respectively. The infant complications occurred in group B, including premature birth in 15 cases, low birth weight in 13 cases, neonatal jaundice in 5 cases and mild asphyxia in 5 cases; while the corresponding cases in group A were 24, 18, 4 and 2 (χ2=11.442, P=0.001; χ2=11.395, P=0.001; χ2=4.664, P= 0.031; χ2=8.035, P=0.005). Conclusion SLE patients whose disease conditions are not well controlled would lead to higher percentage of disease deterioration during pregnancy and worse pregnancy outcomes. Key words: Lupus erythematosus, systemic; Disease progression; Pregnancy outcome

Primary immunodeficiency diseases in Northern Iran

IntroductionPrimary immunodeficiency diseases (PID) are a heterogeneous group of inherited disorders, characterised by recurrent severe infections, autoimmunity and lymphoproliferation. Despite impressive progress in identification of novel PID, there is an unfortunate lack of awareness among physicians in identification of patients with PID, especially in non-capital cities of countries worldwide. ResultThis study was performed in a single-centre paediatric hospital in Northern Iran during a 21-year period (1994–2015). Ninety-four patients were included in this study. The majority of cases had antibody deficiencies (37.23%), followed by well-defined syndromes with immunodeficiency in 16 (17.02%), phagocytic disorders in 15 patients (15.95%), complement deficiencies in 15 patients (15.95%), immunodeficiencies affecting cellular and humoral immunity in nine patients (9.57%), disease of immune dysregulation in three (3.19%), and defects in intrinsic and innate immunity in one (1.06%). ConclusionIt seems that there are major variations in frequency of different types of PID in different regions of a country. Therefore, reporting local data could provide better ideas to improve the local health care system strategists and quality of care of PID patients.

Diagnosis of primary antibody and complement deficiencies in young adults after a first invasive bacterial infection

ObjectivesScreening for primary immunodeficiencies (PIDs) in adults is recommended after two severe bacterial infections. We aimed to evaluate if screening should be performed after the first invasive infection in young adults. MethodsEligible patients were retrospectively identified using hospital discharge and bacteriology databases in three centres during a 3-year period. Eighteen to 40-year-old patients were included if they had experienced an invasive infection with encapsulated bacteria commonly encountered in PIDs (Streptococcus pneumoniae (SP), Neisseria meningitidis (NM), Neisseria gonorrhoeae (NG), Haemophilus influenzae (HI), or group A Streptococcus (GAS)). They were excluded in case of general or local predisposing factors. Immunological explorations and PIDs diagnoses were retrieved from medical records. Serum complement and IgG/A/M testings were systematically proposed at the time of study to patients with previously incomplete PID screening. ResultsThe study population comprised 38 patients. Thirty-six had experienced a first invasive episode and a PID was diagnosed in seven (19%): two cases of common variable immunodeficiency revealed by SP bacteraemia, one case of idiopathic primary hypogammaglobulinaemia, and two cases of complement (C6 and C7) deficiency revealed by NM meningitis, one case of IgG2/IgG4 subclasses deficiency revealed by GAS bacteraemia, and one case of specific polysaccharide antibody deficiency revealed by HI meningitis. Two patients had previously experienced an invasive infection before the study period: in both cases, a complement deficiency was diagnosed after a second NM meningitis and a second NG bacteraemia, respectively. ConclusionPID screening should be considered after a first unexplained invasive encapsulated-bacterial infection in young adults.

A microplate assay to measure classical and alternative complement activity.

We developed and validated a kinetic microplate hemolytic assay (HA) to quantify classical and alternative complement activity in a single dilution of human plasma or serum. The assay is based on monitoring hemolysis of sensitized sheep (or uncoated rabbit) red blood cells by means of a 96-well microplate reader. The activity of the calibrator was evaluated by reference to 200 healthy adults. The conversion of 50% hemolysis time into a percentage of activity was obtained using a calibration curve plotted daily. The linearity of the assay as well as interference (by hemolysis, bilrubinemia and lipemia) was assessed for classical pathway (CP). The within-day and the between-day precision was satisfactory regarding the performance of commercially available liposome immunoassay (LIA) and ELISA. Patients with hereditary or acquired complement deficiencies were detected (activity was measured <30%). We also provided a reference range obtained from 200 blood donors. The agreement of CP evaluated on samples from 48 patients was 94% with LIA and 87.5% with ELISA. The sensitivity of our assay was better than that of LIA, and the cost was lower than either LIA or ELISA. In addition, this assay was less time consuming than previously reported HAs. This assay allows the simultaneous measurement of 36 samples in duplicate per run of a 96-well plate. The use of a daily calibration curve allows standardization of the method and leads to good reproducibility. The same technique was also adapted for the quantification of alternative pathway (AP) activity.

Hypersensitivity to Aspirin as a Factor for Poor Control in Hereditary Angioedema

Background: Hereditary angioedema (HAE) is a primary immunodeficiency disorder characterized by C1 complement inhibitor deficiency and unregulated activation of complement. Aspirin hypersensitivity is related to an increase in the amount of leukotrienes with eosinophil and mast cell activation and increased levels of glandular kallikrein with upregulated local conversion of bradykinin. Both conditions can be present in the same patient. Objectives: We present five patients with HAE; they were all being treated in similar ways according to the therapeuthic options available in our institute (danazol). However, three of them had recurrent episodes of angioedema; in these cases, it was identified aspirin hypersensitivity as a cause of poor disease control. A review of the literature is included. Case Presentation: We present the cases of four females and one male (age range 21 - 58 years) with type I HAE. Subjects were all ISSSTE beneficiaries (state workers) treated at the National Medical Center “20 de Noviembre”. Aspirin hypersensitivity was identified in three patients. Elimination of NSAIDs along with dietary elimination of high salicylate-containing foods improved control of angioedema crisis (severe and/ or recurrent episodes). Discussion: Aspirin hypersensitivity was identified as a factor for poor control in our patients with HAE. Such cases improved with dietary elimination of high salicylate-containing foods and avoidance of NSAIDs. Conclusions: This is the first report of patients with HAE and aspirin hypersensitivity as a cause of poor control. We recommend a deliberate search of these comorbidities, especially in cases of poor disease control. Further studies are needed to continue the investigation on this topic.

P202 A case of a 57-year-old male with complement deficiency

P202 A case of a 57-year-old male with complement deficiency

Systemic lupus erythematosus in Spanish males: a study of the Spanish Rheumatology Society Lupus Registry (RELESSER) cohort.

Objective The objective of this study was to describe the demographic, clinical, and immunological manifestations of systemic lupus erythematosus (SLE) in male patients. Methods A cross-sectional, multicenter study was carried out of 3651 patients (353 men, 9.7%, and 3298 women, 90.2%) diagnosed with SLE, included in the Spanish Rheumatology Society SLE Registry (RELESSER). Results Mean ages (18-92 years) of symptom onset were 37 (SD 17) years (men) and 32 (SD 14) years (women). Male/female ratio was 1/9. Age of onset of symptoms and age at diagnosis were higher in men than in women ( p < 0.001). Males were diagnosed earlier than females (p = 0.04) and had more cardiovascular comorbidities ( p < 0.001). Two hundred and thirty-six males (68%) with SLE required hospitalization in comparison with 1713 females (53%) ( p < 0.001). During follow-up, 208 patients died: 30 men (9.3%) and 178 women (5.9%) ( p = 0.02). As regards clinical manifestations, loss of weight ( p = 0.01), lymphadenopathies ( p = 0.02), and splenomegaly ( p = 0.02) were more common in male patients. Female patients were more likely to have inflammatory rash, alopecia, and arthritis ( p < 0.05). As for lung involvement, men with SLE had more pleural fibrosis ( p < 0.001) and pulmonary embolism ( p = 0.01). However, Raynaud's phenomenon was more common in women (35%) than in men (23.7%) ( p < 0.001); lupus nephritis was more common in men, being present in 155 (44.8%) of males versus 933 (29%) of females ( p < 0.001). Multivariate analysis showed that SLE patients with a high Charlson index (more than 3 points) and age > 50 years had a higher mortality (odds ratios 3.6 and 2.1, respectively). Furthermore, SLE patients who developed pulmonary hemorrhage, pulmonary hypertension, psychiatric involvement, complement deficiency, and hemophagocytic syndrome also had higher mortality, regardless of gender. Conclusion Patients with SLE over the age of 50 years have an increased risk of mortality. In Caucasians, age at diagnosis and symptom onset is higher in men than in women. The diagnostic delay is shorter in men. Male SLE patients present more cardiovascular comorbidities, and also more serositis, adenopathies, splenomegaly, renal involvement, convulsion, thrombosis, and lupus anticoagulant positivity than women.

Primary Immunodeficiency Diseases in Oman: 10-Year Experience in a Tertiary Care Hospital.

Primary immunodeficiency (PID) diseases are rare, complex medical disorders that often are overlooked in clinical settings. There are emerging reports of PID from Middle Eastern populations. This study describes the features of PID patients in a tertiary care setting in Oman and compares them with regional and worldwide reports. Sultan Qaboos University Hospital (SQUH) is an academic tertiary care-level hospital for specialized healthcare, including PID patients. At the time of diagnosis, patients' sociodemographics, clinical features, laboratory investigations, and management were entered in electronic form. This study included patients seen between August 2005 and July 2015. One hundred forty patients were registered with a minimum estimated population prevalence of 7.0/100,000. The male/female ratio was 1.6:1, the median age of onset of symptoms was 8months, and diagnosis was 21months with a delay of 13months. Family history was positive in 44%, consanguinity was present in 76%, death of a previous sibling was present in 36%, and there was an overall mortality in 18%, with an 85% probability of survival 10years following diagnosis. The most common type of immunodeficiency was phagocytic disorders (35.0%), followed by predominantly antibody disorders (20.7%), combined immunodeficiency (17.8%), other well-defined PID syndromes (15.0%), immune dysregulation syndromes (3.5%), complement deficiencies (3.5%), and unclassified immunodeficiency (4.2%). The commonest presenting infection was pneumonia (47.1%). PID is not a rare condition in Oman. The prevalence is in concordance with reports from the region but higher than in Western populations. The findings of the current study would help to improve the awareness and management of, and policy making for PID.

Systemic Lupus Erythematosus: Is It One Disease?

Systemic lupus erythematosus (SLE) is a multisystemic disease with a variety of clinical presentations. Monogenic predisposing conditions to the development of this disease have been described. As examples, an impaired expression of interferon-α regulated genes or complement deficiencies have been reported in patients with SLE, with particular clinical presentations. Those defects present particular presentations and a different severity, making an argument that lupus is not a single disease but many. Treatment could be individualized depending on the underlying defect generating the subtype of the disease.

Systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is an autoimmune disease that can affect many organs, including the skin, joints, the central nervous system and the kidneys. Women of childbearing age and certain racial groups are typically predisposed to developing the condition. Rare, inherited, single-gene complement deficiencies are strongly associated with SLE, but the disease is inherited in a polygenic manner in most patients. Genetic interactions with environmental factors, particularly UV light exposure, Epstein-Barr virus infection and hormonal factors, might initiate the disease, resulting in immune dysregulation at the level of cytokines, T cells, B cells and macrophages. Diagnosis is primarily clinical and remains challenging because of the heterogeneity of SLE. Classification criteria have aided clinical trials, but, despite this, only one drug (that is, belimumab) has been approved for use in SLE in the past 60 years. The 10-year mortality has improved and toxic adverse effects of older medications such as cyclophosphamide and glucocorticoids have been partially offset by newer drugs such as mycophenolate mofetil and glucocorticoid-sparing regimes. However, further improvements have been hampered by the adverse effects of renal and neuropsychiatric involvement and late diagnosis. Adding to this burden is the increased risk of premature cardiovascular disease in SLE together with the risk of infection made worse by immunosuppressive therapy. Challenges remain with treatment-resistant disease and symptoms such as fatigue. Newer therapies may bring hope of better outcomes, and the refinement to stem cell and genetic techniques might offer a cure in the future.

Primary bile acid malabsorption. Histologic and immunologic study in three patients.

Three patients are presented with a history of chronic watery diarrhea due to bile acid malabsorption, proved by the tauro-23[75Se]selena-25 homocholic acid test and an unequivocal response to cholestyramine therapy. Fecal fat tests, Schilling tests, and barium studies of the small intestine and colon were all normal. Jejunal biopsies were normal but multiple biopsies of the terminal ileum, performed by retrograde ileoscopy, showed uniform crypt hyperplastic villous atrophy and features of colonic metaplasia with increased mononuclear infiltration of the lamina propria. All 3 patients demonstrated evidence of abnormal immune function, including the presence of serum autoantibodies, circulating immune complexes, and hypocomplementemia. One patient had Sjögren's syndrome. This disorder, which might be immunologically mediated, should be called primary bile acid malabsorption and should be distinguished from other ileal disorders.

Advisory Committee on Immunization Practices Recommended Immunization Schedules for Persons Aged 0 Through 18 Years—United States, 2016

Each year, the Advisory Committee on Immunization Practices (ACIP)* reviews the recommended immunization schedules for persons aged 0 through 18 years to ensure that the schedules reflect current recommendations for Food and Drug Administration-licensed vaccines. In October 2015, ACIP approved the recommended immunization schedules for persons aged 0 through 18 years for 2016; the 2016 schedules include several changes from the 2015 immunization schedules. For 2016, the figures, footnotes, and tables will be published on the CDC immunization schedule website (http://www.cdc.gov/vaccines/schedules/index.html). This provides readers electronic access to the most current version of the schedules and footnotes on the CDC website. Health care providers are advised to use figures, tables, and the combined footnotes together. Printable versions of the 2016 immunization schedules for persons aged 0 through 18 years in several formats (e.g., portrait, landscape, and pocket-sized versions) and ordering instructions for laminated versions and "parent-friendly" schedules are available at the immunization schedule website.

Infections Revealing Complement Deficiency in Adults

Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies.A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis.Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35% (n = 14/34).This large study emphasizes that complement deficiencies can be revealed in adults by infectious episodes. Most of them were meningococcal infections revealing common final pathway deficiency. To avoid undiagnosis or late diagnosis, adult displaying first episode of N meningitidis infection should be tested for complement deficiency.

Mannose-binding lectin (MBL) is the main complement activator on Aspergillus fumigatus conidia under immunocompromised conditions

Abstract Aspergillus fumigatus is normally a non-pathogenic fungus, but in immunocompromised patients this fungus becomes highly pathogenic. Complement activation are thought to be of crucial importance for elimination of A. fumigatus. However, which of the three complement pathways that are important under immunocompromised conditions are only partly understood. Conidia from a clinical isolate of A. fumigatus were co-incubated with serum before complement activation products C4b, C3b and TCC were measured in flow cytometry. Besides normal (NHS) and complement deficient sera plus complement inhibitors, we used umbilical cord serum (UCS) to mimic a compromised immune defense reflected in the low immunoglobulin (Ig) levels. In NHS, the classical pathway was the dominant initiator with the alternative pathway providing a strong C3b amplification. Classical pathway is known to be initiated via C1q binding to Ig, whereas MBL and ficolin-2 from the lectin pathway bind the fungus directly. UCS conveyed low IgG and no IgM binding to the conidia, and we observed that complement activation on A. fumigatus in UCS was predominantly MBL dependent. UCS with low MBL had significantly lower C3b deposition than serum from NHS with low MBL. Moreover, a close positive correlation between MBL levels and C3b deposition in UCS (Spearman r = 0.79, p &amp;lt; 0.0001, n = 23) was observed. The significance of MBL was emphasized by decreased neutrophilic phagocytosis of conidia via MBL inhibition in C1q−/− serum. We conclude that MBL is the main complement activator and phagocytosis initiator of A. fumigatus conidia in individuals with low Ig levels. This suggests a crucial role for the lectin pathway in protection against infection of A. fumigatus in immunocompromised patients.