Immunoglobulin M Deficiency Publications (2457)
Immunoglobulin M Deficiency Publications
To identify the mechanisms by which sIgM deficiency accelerates atherosclerosis in mice.
We here show that both sIgM(-/-) and Ldlr(-/-)sIgM(-/-) mice develop increased plasma IgE titers because of impaired generation of B cells expressing the low-affinity IgE receptor CD23, which mediates the clearance of IgE antibodies. We further report that Ldlr(-/-)sIgM(-/-) mice exhibit increased numbers of activated mast cells and neutrophils in the perivascular area of atherosclerotic plaques. Treatment with an anti-IgE-neutralizing antibody fully reversed vascular inflammation and accelerated atherosclerotic lesion formation in cholesterol-fed Ldlr(-/-)sIgM(-/-) mice.
Thus, our data identify a previously unsuspected mechanism by which sIgM deficiency aggravates atherosclerosis.
We designated these mice BCL2(+)IL6(+)AID(-) and found that they developed-with full genetic penetrance (100% incidence) and suitably short latency (93 days median survival)-a severe IgM(+) lymphoproliferative disorder that recapitulated important features of human WM. However, the BCL2(+)IL6(+)AID(-) model also exhibited shortcomings, such as low serum IgM levels and histopathological changes not seen in patients with WM, collectively indicating that further refinements of the model are required to achieve better correlations with disease characteristics of WM.
The patient underwent Ig replacement therapy and received growth hormone therapy in addition to antibiotics and responded well. Furthermore, the patient developed benign cervical lymphadenopathy, as well as elevated erythrocyte sedimentation rate, positive autoantibodies to SSA-Ro, and severely dry eyes, which partially responded to both the punctate occlusion and systemic corticosteroids, at the age of seven years. Sequencing analysis of the exons from activation-induced cytidine deaminase (AICDA) gene revealed that the patient was homozygous for a single T to C transversion at position 455 in exon 4, which replaces a Valine with an Alanine.
To our knowledge, this is a new AICDA mutation, which has not been reported previously in HIGM. The mutation analysis could improve diagnosis of HIGM patients and also elaborating on the spectrum of AICDA mutations.
sIgMD may occur as a primary or secondary condition. sIgMD is much more common than primary .Hemophagocytic lymphohistiocytosis (HLH) is also a rare but potentially fatal disease of normal but overactive histiocytes and lymphocytes and can be primary or secondary, characterized by the overwhelming activation of normal T lymphocytes and macrophages, invariably leading to clinical and hematologic alterations. We report an adult case of primary sIgMD with absent B lymphoid cells and secondary HLH syndrome who presented with recurrent infections, fever and pancytopenia.
Patients may be asymptomatic or else present with recurrent infection, autoimmunity, atopic disease and/or malignancy. About 50% of patients with symptomatic SIgMD also have impaired antibody responses to the pneumococcal polysaccharide vaccine. We report on an adult who presented with symptomatic SIgMD with impaired pneumococcal polysaccharide antibody responses and lymphopenia, who experienced a significant clinical improvement in the frequency of infections after subcutaneous immunoglobulin replacement therapy.
Patients were assessed if venous thromboembolism occurred within 6 months after knee arthroscopy (n=10) or total hip or knee arthroplasty (n=21). This study assessed gene mutations (factor V Leiden, prothrombin G20210A, plasminogen activator inhibitor, methylenetetrahydrofolate reductase) and serologic thrombophilias (high levels of factors VIII and XI, homocysteine, anticardiolipin immunoglobulin G and immunoglobulin M antibodies, and lupus anticoagulant; low antigenic protein C, S, and free S; and antithrombin III deficiency). The same coagulation data were obtained for normal subjects (n=110). The major thrombophilias in the arthroscopy group were factor V Leiden heterozygosity (40%), high factor VIII level (50%), and high homocysteine (30%). The respective values in control subjects were 2% (P=.0004), 7% (P=.0011), and 5% (P=.02). When the arthroscopy group was compared with the 21 patients who had venous thromboembolism after total hip or knee arthroplasty, the sole difference was factor V Leiden heterozygosity, which was 40% vs 0%, respectively (P=.007). Although venous thromboembolism after knee arthroscopy is uncommon, to identify high-risk patients and guide postoperative thromboprophylaxis, the authors suggest routine preoperative measurement of 3 common familial thrombophilias: factor V Leiden, factor VIII, and homocysteine. [Orthopedics. 2016; 39(6):e1052-e1057.].
Detection of antibodies of PVB19 was done by enzyme-linked immunosorbent assay (Elisa). In our study, prevalence of immunoglobulin G (IgG) and IgM were 44 and 11.3%, respectively. Clinically, children with positive IgM serology had submitted an erythema infectiosum (13/29 cases), myocarditis (1 case), encephalitis (1 case), severe sickle cell anemia (7 cases), and immunocompromised (7 cases). The incidence rate of viral infection was 11.3%; most of the cases of PVB19 infection occurred between the months of May and August. Incidence was higher in the 10-15 years age group (21%). The prevalence of IgG antibody varied and increased with age, it rises from 38.2% in preschool children (19 months-4 years) to 53.5% in those aged between 4.5 and 15 years, reaching 58% in the 10-15 years age group. The four risk factors of PVB19 infection are: (1) those aged between 4.5 and 9 years, which is the most affected age group (P = 0.0018); (2) female gender in children aged between 19 months and 4 years (P = 0.037); (3) transfusion and (4) immune deficiency (P = 0.022 and P = 0.001, respectively). The study of the prevalence of PVB19 infection shows that viral infection is acquired early in childhood, increases with age; viral transmission is favored by the community life. Because of the widespread vaccination program against measles and rubella, the systematic search of PVB19 in front of eruptive fevers becomes important.
The frequency of C104R monoallelic-mutations was not higher than that found in healthy controls. Biallelic-mutations were exclusively found in CVID. CVID patients carrying monoallelic-mutations had an increased prevalence of lymphadenopathy, granulomata, and autoimmune cytopenias. CVID carrying biallelic-mutations had a low prevalence of autoimmunity in comparison with TACI wild-type CVID. Moreover, biallelic-mutated CVID had higher frequency of switched memory B-cells and higher IgM and IgA antibodies to polysaccharide antigens than TACI wild-type and monoallelic-mutated CVID. TACI-mutated IgAD patients had only monoallelic-mutations and did not display clinical difference from IgAD wild-type patients. In conclusion, TNFRSF13B genetic screening of antibody deficiencies may allow the identification of mutational patterns. However, as with counseling for risk assessment, geneticists should be aware that the interpretation of genetic testing for TACI mutations is difficult and the potential impact on clinical management is still limited.
Associated disorders included the following: autoimmune conditions 50.0%; hypothyroidism 24.1%; atopy 38.9%; and other allergy 31.5%. In 35.5%, proportions of protective S. pneumoniae serotype-specific IgG levels did not increase after polyvalent pneumococcal polysaccharide vaccination (PPPV). Blood lymphocyte subset levels were within reference limits in most patients. Regressions on IgG1 and IgG3 revealed no significant association with age, sex, autoimmune conditions, hypothyroidism, atopy, other allergy, corticosteroid therapy, or lymphocyte subsets. Regression on IgG2 revealed significant associations with PPPV response (negative) and CD19+ lymphocytes (positive). Regression on IgG4 revealed significant positive associations with episodic corticosteroid use and IgA. Regression on IgA revealed positive associations with IgG2 and IgG4. Regression on IgM revealed negative associations with CD56+/CD16+ lymphocytes. Regressions on categories of infection revealed a negative association of urinary tract infections and IgG1. HLA-A(⁎)03, HLA-B(⁎)55 and HLA-A(⁎)24, HLA-B(⁎)35 haplotype frequencies were greater in 38 patients than 751 controls. We conclude that nonprotective S. pneumoniae IgG levels and atopy contribute to increased susceptibility to respiratory tract infections in patients with selective subnormal IgG1.
Here, we show that deficiency of Siglec-G in atherosclerosis-prone mice inhibits plaque formation and diet-induced hepatic inflammation. We further demonstrate that selective deficiency of Siglec-G in B cells alone is sufficient to mediate these effects. Levels of B-1 cell-derived natural IgM with specificity for OxLDL were significantly increased in the plasma and peritoneal cavity of Siglec-G-deficient mice. Consistent with the neutralizing functions of OxLDL-specific IgM, Siglec-G-deficient mice were protected from OxLDL-induced sterile inflammation. Thus, Siglec-G promotes atherosclerosis and hepatic inflammation by suppressing protective anti-inflammatory effector functions of B cells.