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Background: Patients with chronic rhinosinusitis (CRS) and immunoglobulin deficiencies (ID) have more recalcitrant sinonasal disease and a subset of these patients undergo surgical management for their CRS. However, there is a paucity of literature on the surgical outcomes in this patient population and appropriate treatment algorithms for CRS in patients with ID. The objective of this study was to better elucidate the outcomes of endoscopic sinus surgery (ESS) in patients with ID in terms of disease-specific quality-of-life scores and the need for revision surgery., Methods: A case-control study was performed comparing adult patients with ID and healthy controls that had undergone ESS for CRS. Patients were matched based on age, sex, CRS phenotype, and preoperative Lund-Mackay score. The revision surgery rates, time to revision surgery, and changes in sinonasal outcome tests (SNOT-22) were evaluated., Results: Thirteen patients with CRS and ID were matched to 26 control patients with CRS. The revision surgery rate for cases and controls was 31% and 12%, respectively, but there was no statistical difference (p > 0.05). There was a clinically meaningful reduction in SNOT-22 scores in both groups from the preoperative to postoperative period [mean of 12 points in patients with ID (p = 0.323) and 25 points in controls (p < 0.001)], however, there was again no significant difference between cases and controls (p > 0.05)., Conclusion: Our data suggests that patients with ID have clinically meaningful improvement in SNOT-22 scores after ESS but may have higher revision rates than immunocompetent patients with CRS. ID are rare disease entities, thus most attempts at studying this cohort would be limited by sample size. Further homogenous data on immunoglobulin deficient patients is required for future meta-analysis to better understand the impact of ESS in patients with ID., (© 2023. The Author(s).)

Background: Patients with primary antibody deficiencies have an increased frequency of sinonasal and pulmonary infections. Immunoglobulin (Ig) replacement is a standard therapy for common variable immunodeficiency (CVID) and other antibody deficiency diseases. Although there is convincing evidence that Ig replacement reduces pulmonary infections, there is little evidence that it reduces sinus infections or abates chronic rhinosinusitis (CRS). This study aims to identify the impact of Ig replacement on CRS in antibody deficiencies., Methods: A single-center, retrospective chart review of adult patients from 1995 to 2015 was performed. Inclusion criteria were diagnosis of CVID or specific antibody deficiency (SAD), history of CRS requiring medical and/or surgical management within the year prior to presentation, treatment with Ig replacement therapy, and follow-up interval of at least 1 year after initiating Ig replacement. Patients with secondary immune deficiencies were excluded. Thirty-one patients met criteria. Data collected included pretreatment and posttreatment Lund-Mackay scores, and frequency of sinusitis and pulmonary infections requiring rescue antibiotics. Statistical analysis was performed using Wilcoxon signed-rank tests., Results: A significant decline in the Lund-Mackay score was evidenced from pretreatment to posttreatment (p < 0.01). Treatment also resulted in significantly lower rates of sinusitis (p < 0.01) and pulmonary infections (p < 0.01). Additionally, 56% of patients who were on prophylactic antibiotics prior to Ig replacement were able to discontinue their use., Conclusion: We present objective evidence showing that Ig replacement therapy has a positive impact on the frequency of sinusitis and confirm its positive impact on pulmonary infections in adult patients with CVID and SAD., (© 2016 ARS-AAOA, LLC.)

Background: Chronic urticaria can be the initial clinical presentation of a number of different diseases. The objective of the present study was to report the associated diseases during a ten-year clinical-laboratory follow-up in patients with an initial diagnosis of chronic spontaneous urticaria (CSU) of unknown cause., Methods: A prospective, longitudinal cohort study with a ten-year clinical-laboratory follow-up was conducted. Patients with a history of urticarial plaques of over six weeks presenting as the only clinical symptom were selected. Individuals with other clinical conditions, urticaria of known causes or chronic physical urticaria were excluded. The following tests were initially performed: haemogram, urine type I, stool parasite exam and sedimentation rate. The following exams were ordered during follow-up: PPD; urine culture; serology tests; antithyroid and antinuclear antibodies, rheumatoid factor, lupus anticoagulant; thyroid hormones; serum immunoglobulin; paranasal sinus and thorax radiographs; testing for BK and Helicobacter pylori; and prick tests., Results: Infections were diagnosed in 29% of patients (syphilis, parasitosis, H. pylori, urinary infection, tuberculosis, hepatitis B and C); autoimmune diseases in 21% (thyroiditis, rheumatoid arthritis and antiphospholipid antibody syndrome); primary immunodeficiencies in 4% (IgA and IgG2 deficiencies); and chronic myeloid leukaemia in 1%. At ten-years of follow-up, the urticaria diagnosis was CSU of unknown cause in 45% of the cases., Conclusion: This ten-year clinical-laboratory follow-up of 100 individuals with chronic urticaria as the initial diagnosis revealed the presence of associated diseases in over half of the cases. The most prevalent diseases were infections and autoimmune diseases besides primary immunodeficiencies and blood diseases., (Copyright © 2016 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.)

Selective immunoglobulin M deficiency(sIgMD) is a rare form of dysgammaglobulinaemia characterized by an isolated low level of serum immunoglobulin M (IgM). It was an incidence of less than 0.03% in the general population and 1% in hospitalized patients. 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., (© Journal of the Association of Physicians of India 2011.)

Selective immunoglobulin M (SIgM) deficiency is a rare form of dysgammaglobulinemia. Here we are reporting a 31year old man with multiple cervical and testicular abscesses who was investigated and found to have miliary tuberculosis (MTB) with primary SIgM deficiency (Serum IgM: 17.4mg/dL) and was treated aggressively with anti-tuberculous treatment., (Copyright © 2015 Asian-African Society for Mycobacteriology. Published by Elsevier Ltd. All rights reserved.)

Selective immunoglobulin E (IgE) deficiency (IgED) is defined as serum levels of IgE more than or equal to 2 kIU/L and is associated with immune dysregulation and autoimmunity. This study aimed to investigate a prevalence of atherosclerotic cardiovascular disease (ASCVD) in population with IgED. Within the electronic patient record (EPR) database of Leumit Health Care Services (LHS) in Israel, data capture was performed using IBM Cognos 10.1.1 BI Report Studio software. The case samples were drawn from the full study population (n = 18,487), having any allergy-related symptoms and/or those requesting antiallergy medications and performed serum total IgE measurement during 2012 at LHS. All subjects aged more than or equal to 40 years old, with serum total IgE less than 2 kIU/L were included in case group. Control group was randomly sampled from the remained subjects, with a case-control ratio of 10 controls for each case (1:10). The comorbid cardiovascular diseases during less than or equal to 10 years before serum total IgE testing were identified and retrieved using specific International Classification of Diseases, 9th Revision, Clinical Modification diagnostic codes. There were 103 in case and 1030 subjects in control group. Compared with control group patients, the case group had significantly more arterial hypertension [34 (37.7%) versus 187 (18.2%), p < 0.001], ischemic heart disease (IHD) [26 (25.2%) versus 87 (8.4%), p < 0.001], carotid stenosis [5 (4.9%) versus 7 (0.7%), p = 0.003], cerebrovascular disease (CVD) [3 (2.9%) versus 5 (0.5%), p = 0.029], and peripheral vascular disease (PVD) [4 (3.9%) versus 9 (0.9%), p = 0.024]. IgED is associated with higher prevalence of arterial hypertension and ASCVD.

Humoral immunodeficiency disorders present in children after 6 months of age with recurrent respiratory and gastrointestinal infections. These may be due to the absence of B cells causing panhypogammaglobulinaemia, or due to selective deficiencies in immunoglobulin subfractions. We present the case of a child with selective deficiency of IgM and IgG4 resulting in chronic diarrhoea and recurrent lower respiratory infections. With appropriate treatment of infections, the child had good symptom relief. Such an unusual combination of antibody deficiency has not been previously described in children. This case serves to illustrate the need for awareness to institute timely therapy for infection along with appropriate prophylactic measures like vaccination for these children., (2014 BMJ Publishing Group Ltd.)

Immunoglobulin M (IgM) provides the initial response to foreign antigen and plays a regulatory role in subsequent immune response development, accelerating the production of high-affinity IgG. Though selective IgM deficiency was described more than 45 years ago in children with fulminant meningococcal septicemia, it has been largely an ignored primary immunodeficiency. It appears to be more common than originally realized. Selective IgM deficiency is observed in both children and adults with no gender bias. The most common clinical manifestation of selective IgM deficiency is infections with extracellular and intracellular bacteria, viruses, and fungi. Allergic diatheses are the second commonest presentation of selective IgM deficiency. There is an increased prevalence of autoimmune diseases, which in both humans and mice appear to be secondary to selective IgM deficiency rather IgM deficiency secondary to autoimmune diseases. Selective IgM deficiency, in some cases, is associated with 22q11.2 chromosome deletion and few familial cases of selective IgM deficiency have been reported. Innate immunity is relatively intact. T cells, T cell subsets, and T cell functions are normal. However, several patients with selective IgM deficiency and T cell and NK cell defects with Mycobacterium avium intracellulare infections have been reported. In a subset of patients with selective IgM deficiency circulating IgM+ B cells are decreased or completely lacking. Specific IgG antibody responses against pneumococcus polysaccharides are impaired in a subset of patients with selective IgM deficiency. The pathogenesis of selective IgM deficiency is unclear; decreased T helper activity, increased isotype-specific suppressor T cell activity, and intrinsic B cell defects have been reported. Patients with selective IgM deficiency and impaired pneumococcal antibody responses appear to respond to immunoglobulin therapy.

Objectives: Immunoglobulin (Ig) deficiency is a well-known risk factor for Streptococcus pneumoniae or Haemophilus influenzae infections and noteworthy invasive diseases. However, the proportion of these deficiencies in cases of invasive disease is unknown. The objective of this study was to evaluate the rate of Ig deficiency in cases of invasive disease., Methods: A prospective study was conducted from January 2008 to October 2010 in two French hospitals. Measurement of Ig levels was carried out in patients hospitalized for invasive diseases., Results: A total of 119 patients were enrolled in the study, with nine cases of H. influenzae and 110 cases of S. pneumoniae invasive disease. There were 18 cases of meningitis, 79 of invasive pneumonia, and 22 other invasive diseases. Forty-five patients (37.8%) had an Ig abnormality, 37 of whom had an Ig deficiency (20 IgG <6g/l, four isolated IgA <0.7g/l, and 13 isolated IgM <0.5g/l), while eight had an elevated monoclonal paraprotein. Nineteen of these 45 patients had a clearly defined Ig abnormality, with five primary deficiencies (three common variable immunodeficiencies and two complete IgA deficiencies) and 14 secondary deficiencies, mainly lymphoproliferative disorders. All these deficiencies were either not known or not substituted., Conclusions: Humoral deficiency is frequent in patients with S. pneumoniae or H. influenzae invasive disease and Ig dosage should be proposed systematically after such infections., (Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Jacobsen syndrome is a rare contiguous gene syndrome caused by partial deletion of the long arm of chromosome 11. The typical clinical manifestations include physical growth retardation, mental retardation,facial dysmorphisms, congenital heart disease, thrombocytopenia, or pancytopenia. A Thai-Australian girl was born with multiple abnormalities. Typical features and her karyotype, 46, XX, del(ll) (q23-qter), confirmed Jacobson syndrome. She had many uncommon findings including upslanting palpebral fissures, tortuousity of retinal vessels and hypogammaglobulinemia. In addition, this case also presented with protein C deficiency, which has not been reported previously in Jacobsen syndrome. The patient was treated with phototherapy, intravenous antibiotic injection, and platelet transfusion in neonatal period. Cranioplasty was performed for prevention of the increased intracranial pressure at three months of age. Surgical correction for strabismus was in the treatment plan.

The diagnosis of Good syndrome is very difficult. It has various symptoms, and these symptoms can be present at different periods. In this report we present a patient with refractory chronic diarrhea, recurrent pneumonia, and dysgammaglobulinemia after thymectomy, who was finally then diagnosed with Good syndrome.

Hypogammaglobulinemia is a common complication of chronic lymphocytic leukemia (CLL), but the significance of immunoglobulin G (IgG) subclass deficiency is unknown. We analyzed the prevalence of immunoglobulins G, A and M, IgG subclass deficiency and infection in 150 patients with CLL. Low IgG, IgA and IgM levels were observed in 27.3%, 30.7% and 56.7% of patients, respectively. IgG subclass deficiency was frequent, with reduced IgG1, IgG2, IgG3 and IgG4 in 28%, 19.3%, 52% and 22.7% of patients, respectively. IgG subclass deficiency (total 64.6%) and hypogammaglobulinemia (27.3%) were more prevalent than clinically significant infection (16%). Recurrent or significant infections were seen in 24 patients (16%), of whom 50% had hypogammaglobulinemia but 100% had at least one IgG subclass deficiency, indicating that half the patients with infection had IgG subclass deficiency but normal total IgG level. Deficiencies of IgG3 and IgG4 were statistically associated with infection risk. Normal immunoglobulin and IgG subclass levels were seen in 26 patients (17%) and none had infections. IgG subclass deficiency is commonly observed in patients with CLL with both normal and reduced total IgG levels, and is associated with infection. Screening patients with CLL for IgG subclass deficiency may be a useful adjunct in stratifying their infection risk.

Immunoglobulin (Ig)D is the major antigen receptor isotype co-expressed with IgM on the surface of most peripheral B cells in mice and humans. However, the biological role of IgD as B cell receptor (BCR) has remained unclear. Previous studies have indicated that IgD may play a role in B cell tolerance. To understand the role of IgD in B cell tolerance and autoimmunity, we have examined the development of autoimmune syndrome in lpr mice deficient for IgD. The present study showed that IgD deficiency did not alter lymphoproliferation and lymphocyte activation in lpr mice. The survival and proliferation of B cells were not affected by the absence of IgD, indicating that IgD BCR-mediated signals do not have an important role in negative selection of autoreactive B cell clones. Interestingly, compared to IgD-competent littermates, lpr mice with IgD deficiency had elevated autoantibody production, increased deposition of immune complex in the kidney and more severe nephritis. Accumulation of abnormal CD4(-) CD8(-) αβ(+) T cells was accelerated in IgD(-/-) lpr mice compared to lpr mice. These results suggest that IgD BCR-mediated signals may be involved in the differentiation of autoreactive B cells into plasma cells and abnormal T cell expansion., (© 2011 The Authors. Clinical and Experimental Immunology © 2011 British Society for Immunology.)

We present a pediatric case of recurrent optic neuritis, celiac disease, partial IgA and IgG3 deficiency in the context of anti-aquaporin-4 auto-immunity and familial IgA deficiency with celiac disease. Treatment with tacrolimus was successful in preventing disease relapses. This case stresses the relevance of central nervous system anti-aquaporin-4 auto-immunity in a broader context of immune dysregulation and neuro-immunology., (Copyright © 2010 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Selective immunoglobulin M (IgM) deficiency is a rare disorder defined by a decreased serum level of IgM and normal levels of other immunoglobulin classes. The disease has not been well described and the cause remains unknown. Patients with IgM deficiency may present with a wide spectrum of clinical manifestations, from asymptomatic to life-threatening infections, including recurrent respiratory and gastrointestinal infections, allergy and autoimmunity. Here, we report a 6.5-year-old otherwise healthy boy with selective IgM deficiency who presented with multiple recurrent impetigo. We reviewed the published data regarding selective deficiency of IgM.

Objective: Limited information exists on features of pediatric Selective IgM immunodeficiency (SIgMID). Previously published pediatric cases and 2 new cases are reviewed., Methods: English literature from PubMed and references from relevant articles were reviewed. Previously reported cases and 2 new cases from an allergy/immunology practice were analyzed., Results: Forty-nine reported cases of SIgMID presented with respiratory infections (77.6%), gastrointestinal disease (16.3%), skin disease (12.2%), and meningitis (8.2%). Mean serum IgM level was 16.5+/-13.8 mg/dL. Two patients were identified with SIgMID among 6300 active pediatric patients (0.03%) presenting with asthma, vasomotor rhinitis, and recurrent respiratory infections. In the 51 cases reported, none developed lymphoproliferative disease nor evolved into panhypogammaglobulinemia; four fatalities were reported., Conclusions: The prevalence of SIgMID in our pediatric population was 0.03%. In general, respiratory infections are the common comorbid conditions. Death and autoimmune disease are uncommon complications of pediatric SIgMID.

Primary selective immunoglobulin (Ig) M deficiency usually presents early in life with recurrent or severe infections caused by encapsulated and gram-negative organisms. Primary selective IgM deficiency in adults is rare and is usually associated with autoimmune diseases or malignant neoplasm. We performed an extensive immunological analysis of innate and adaptive immunity in an adult patient with possible primary selective IgM deficiency who presented with life-threatening Streptococcus pneumoniae septic shock and invasive Aspergillus fumigatus infection. The patient had no evidence of autoimmune disease or malignant neoplasm. Serum IgG, IgA, and IgE were normal; however, serum IgM levels and specific antibody titers against all 14 pneumococcal polysaccharide serotypes were consistently low. Complement CH50, C3, C4, and neutrophil phagocytosis and oxidative burst were normal. Toll-like receptor expression on monocytes was also normal. Therefore, adult patients with serious life-threatening and unusual infections should be investigated for possible selective primary IgM deficiency.

Common variable immune deficiency (CVID) is associated with autoimmune and inflammatory complications in addition to recurrent infections. The most common conditions are idiopathic thrombocytopenia purpura, autoimmune hemolytic anemia, sarcoid-like granulomatous disease and gastrointestinal inflammation. IVIG administration reduces the frequency of infections, but does not always prevent autoimmunity or inflammation. TNF antagonists and anti-CD20 immunomodulators have shown some efficacy in CVID in a few patients; further controlled studies are needed to determine the best management of these conditions in the setting of immunodeficiency.

More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A(-/-) mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in SH2D1A(-/-) mice upon primary immunization, and because SH2D1A was detectable in wt germinal center B cells, we examined whether SH2D1A(-/-) B cell functions were impaired. Using the adoptive cotransfer of B lymphocytes from hapten-primed SH2D1A(-/-) mice with CD4(+) T cells from primed wt mice into irradiated wt mice provided evidence that signal transduction events controlled by SH2D1A are essential for B cell activities resulting in antigen specific IgG production. Defects in naive SH2D1A(-/-) B cells became evident upon cotransfer with non-primed wt CD4(+) cells into Rag2(-/-) recipients. Thus, both defective T and B cells exist in the absence of SH2D1A, which may explain the progressive dysgammaglobulinemia in a subset of X-linked lympho-proliferative disease patients without involvement of Epstein-Barr virus.

We report the case of an 18-month-old girl who died of overwhelming pneumococcal sepsis. Autopsy revealed a small spleen with unusual architecture. There was a marked rarefaction of the white pulp with only very few but florid germinal centers. Immunohistochemical staining showed a low number of T and B lymphocytes in the spleen, whereas normal numbers and distribution of lymphocytes were found in all other primary and secondary lymphatic organs. Whereas levels of IgM were normal, IgA and IgG levels were significantly lower than in age-matched controls. Consistent with serological data, B cells mainly expressed IgM and IgD, whereas IgG expression was lower than expected. Additionally, intestinal immunoglobulin distribution in B-cell areas of lymphofollicular hyperplasia showed normal expression of IgM, but almost no expression of IgA. A review of the literature failed to disclose a similar case of dysgammaglobulinemia associated with isolated structural spleen anomalies. We propose that the patient suffered from a defect of the B-cell differentiation pathway.

Hyper-IgM syndrome is a rare immunodeficiency disease characterized by markedly decreased serum IgG, IgA, and IgE levels but normal or elevated IgM levels. The most common clinical signs are infections, cirrhosis, arthritis, malignancies, and mucosal ulcers. Approximately two-thirds of patients have chronic neutropenia associated with oral and perirectal ulcers. We report a 14-month-old girl with hyper-IgM syndrome who has recurrent cutaneous ulcers restricted to the diaper area.

J-chain-deficient (Jch(-/-)) mice were used to study the role of polymeric IgA (pIgA) in primary disease and protective immunity following genital herpes simplex type 2 (HSV-2) infection. Vaginal IgA in the Jch(-/-) mice was composed primarily of monomeric IgA and was not associated with secretory component (SC). In contrast, vaginal IgA in wild-type (WT) mice was predominantly polymeric and bound to SC. Following HSV-2 genital infection, the Jch(-/-) mice consistently exhibited fewer vaginal symptoms (P = 0.010) and mortality (P = 0.075) than did the WT mice. The variation in disease expression could not be explained by differences in local viral replication, since titers in vaginal wash fluid were comparable. To assess the effect of J chain deficiency on protective immunity, WT and Jch(-/-) mice were immunized intravaginally with attenuated HSV-2, challenged intravaginally with wild-type virus 5 weeks later, and evaluated for vaginal infection and neurological disease. Although the Jch(-/-) mice had reduced vaginal HSV-specific IgA and IgG levels following immunization, both WT and Jch(-/-) mice were protected from symptoms following wild-type virus challenge. We conclude that pIgA is not required for protective immunity against genital HSV-2 disease and that J chain deficiency offers some protection against symptoms following primary HSV-2 genital infection., (Copyright 2000 Academic Press.)

X-linked lymphoproliferative disease (XLP) is a primary immunodeficiency, which most often manifests itself after Epstein-Barr virus (EBV) infection. The main clinical phenotypes include fulminant or fatal infectious mononucleosis, dysgammaglobulinaemia and malignant lymphoma. We have recently cloned the SH2D1A gene, which has been shown to be mutated in approximately 70% of XLP patients. Now we report five novel SH2D1A mutations in patients from five unrelated XLP families. No mutations were found in another three XLP families. In three boys with early onset non-Hodgkin lymphoma (NHL) from two unrelated families a deletion of SH2D1A exon 1 and a splice site mutation were found, respectively. These patients did not show any laboratory or clinical signs of a previous EBV infection. A fourth EBV-uninfected and unrelated boy with a stop mutation in the SH2D1A gene shows only signs of dysgammaglobulinaemia. Development of dysgamma-globulinaemia and lymphoma without evidence of prior EBV infection in four of our patients suggests that EBV is unrelated to these phenotypes, in contrast to fulminant or fatal infectious mononucleosis. The role of SH2D1A as a putative tumour suppressor gene remains to be investigated.

Mycobacterium avium-intracellulare (MAI) is a ubiquitous organism with limited virulence in the immunocompetent host. Disseminated disease is associated with a high mortality rate. Except for localized cervical adenitis, MAI disease is rare in immunocompetent children. We report a child with antibody deficiency (dysgammaglobulinemia) and disseminated MAI infection, in whom complete, long-term remission was attained with multiple antimycobacterial therapy. The patient presented with progressive cervical lymphadenopathy and hepatomegaly at 7 years of age. A lymph node biopsy showed acid-fast bacilli and granulomas. Despite a transient response to conventional antituberculous therapy, including isoniazid and rifampin, his symptoms progressed. Cultures from blood, bone marrow, spleen, and cervical lymph node tissues revealed an MAI organism. Subsequent treatment using a combination of clarithromycin, amikacin, and ethambutol for 16 months resolved clinical symptoms, and subsequent blood culture results became negative. By the time of this report, the patient has been disease-free for 4 years. Multiple-drug therapy is promising for the treatment of MAI in children with antibody deficiency; however, the selection of antiinfective drugs should include a member of the newer macrolide family. acquired immunodeficiency syndrome, clarithromycin, dysgammaglobulinemia, Mycobacterium avium-intracellulare, treatment.

Background: Clinical features of Jacobsen syndrome include facial dysmorphism, congenital heart defects, digit anomalies and mild to moderate psychomotor retardation. Thrombocytopenia or pancytopenia is observed in one half of patients., Patients: Two unrelated children, a 6-month- and a 12-year-old, presented with a moderate thrombocytopenia associated with the clinical features of Jacobsen syndrome. Bone marrow aspirates showed, in both patients, normal cellularity with an increased number of micromegacaryocytes. Chromosome analysis showed a partial deletion of the long arm of chromosome 11. The 12-year-old patient had a history of upper respiratory airways infections with immune humoral deficiency (decreased level of IgA and IgM) which, to our knowledge, has never been reported., Conclusion: Jacobsen syndrome is a cause of inherited thrombocytopenia in children. Humoral immune functions must be explored in patients with a history of repeated infections.

Background: The recurrent pyogenic infections of patients with hyper-IgM syndrome are controlled by intravenous gamma globulin administration, but patients may suffer from early-onset oral ulcerations and warts., Objective: We have characterized the mucocutaneous manifestations associated with this condition to allow physicians to more readily identify it., Methods: Three male patients with the mucocutaneous manifestations of the hyper-IgM syndrome are described. In one, histopathologic examination of the oral mucosal lesion was performed., Results: Recurrent large, painful oral ulcerations can occur that are not necessarily associated with neutropenia nor do they respond to granulocyte colony-stimulating factor administration. Histopathologic examination of an ulcer showed a heavy infiltrate of mixed inflammatory cells. Warts tend to be widespread and resistant to traditional therapy., Conclusion: Physicians should consider this uncommon condition when examining a male patient with severe oral ulcers or recalcitrant widespread warts.

The immunoglobulin E (IgE) response, a hallmark of helminthic infection, is generally considered a major host defense against schistosomiasis mansoni. In support, it was reported that mice with a null mutation of the Ce gene, which are thus incapable of making IgE, developed Schistosoma mansoni worm burdens 2-fold greater than wild-type mice. However, in another study, reduction of the IgE response in mice to a primary S. mansoni infection by anti-IgE treatment resulted in decreased worm burden and fecundity, suggesting that IgE plays a detrimental, rather than beneficial, role for the host in schistosomiasis. In a third study, S. mansoni worm burden and egg production in normal and in IL-4-deficient mice that produce negligible IgE levels did not differ significantly, and it appeared that IgE did not affect parasite survival or fecundity. In an attempt to resolve these controversies, we examined hepatic worm load and egg production in the liver and small intestine of IgE-deficient (SJA/9) and control IgE-producing (SJL/J) mice, 8 wk after S. mansoni infection. No differences were observed in worm burden, total egg production, and number of eggs produced per female worm in the 2 mouse strains, confirming the data that imply that IgE does not play an essential role in primary S. mansoni infection.

Forty two infants below the age of 2 years presenting with chronic non-infective diarrhoea and shown to have histologically proved colitis were investigated over a five year period. Allergic colitis was the most common cause of colitis, accounting for 62% of the cases. Other colitides diagnosed included: non-specific colitis, autoimmune enterocolitis, and ulcerative colitis accounting for 10% each; severe combined immunodeficiency 7%, and Crohn's disease 3%. A positive family history and a personal history of atopy were obtained in 48% and 29% of the cases respectively. Serum immunoglobulin A, IgG2, and IgG4 were very low in over 50% of the entire cohort of infants with colitis; 66% of those with severe combined immunodeficiency, autoimmune enterocolitis, and ulcerative colitis (n = 11) had low CD3 and CD4 T lymphocytes with an accompanying increase in CD8 in two thirds of those with severe combined immunodeficiency. T lymphocytes were normal in those with allergic colitis. Thus infants with proved non-infective colitis as a group show a high prevalence of IgA, IgG2, and IgG4 deficiency. It is likely that this minor deficiency of mucosa associated immunoglobulin production has a role in the pathogenesis of the colitic process.

The hypothesis that crescent formation in glomerulonephritis (GN) is a delayed type hypersensitivity (DTH)-like lesion, not dependent on a humoral immune response, was addressed using mice with deletion of the mu immunoglobulin heavy chain gene (mu chain deficient mice). Homozygous mu chain deficient mice do not develop mature B cells or produce immunoglobulin, but have intact cell mediated immunity. GN was induced in sensitized mice by a subnephritogenic dose of sheep anti-mouse GBM globulin. Heterozygous mice (mu chain +/-) demonstrated normal antibody and DTH responses to sheep globulin and developed a proliferative GN with proteinuria (6.4 +/- 1.4 mg/24 hr), renal impairment (serum creatinine 32.6 +/- 3.3 mumol/liter) and crescents in 33 +/- 24% of glomeruli, when this antigen was planted in their glomeruli. This lesion was demonstrated to be T cell dependent by in vivo T cell depletion. Homozygous mu chain deficient mice (-/-) also developed proliferative GN, histologically indistinguishable from +/- mice. Proteinuria (3.8 +/- 1.0 mg/24 hr), renal impairment (serum creatinine 24.5 +/- 3.4 mumol/liter) and crescent formation (29 +/- 2% of glomeruli) were no different from =/- mice. Mouse immunoglobulin was absent in their serum and glomeruli, however, cutaneous DTH to sheep globulin was identical to heterozygous mice. These results demonstrate that glomerular crescent formation and injury can occur independent of a humoral immune response to planted glomerular antigen and without glomerular deposition of autologous antibody. This strongly supports the hypothesis that crescent formation is a manifestation of DTH.

We report two cases of bone and joint amyloidosis involvement related to plasma cell dyscrasia. The radiographic appearances mimic numerous benign or malignant diseases. MR imaging shows a diffuse low signal in T1 and an heterogeneous low or mild low signal in T2 weighted spin-echo sequence.

The frequency of humoral immunodeficiencies was analysed in 39 patients with a history of recurrent (> or = 3) episodes of community-acquired pneumonia. Total immunoglobulin levels and/or IgG subclass levels were low in 14 patients (36%), including eight patients with IgG or IgG2 deficiency. The specific antibody activity to pneumococcal capsular polysaccharides (serotypes 3, 6A, 19F, and 23F) and to phosphorylcholine was low in the IgG/IgG2-deficient patients compared to 36 healthy controls, and they also responded poorly to vaccination with a 23-valent pneumococcal capsular polysaccharide vaccine. The remaining 25 patients, with normal immunoglobulin and IgG subclass levels, had specific anti-pneumococcal antibody levels comparable to the healthy controls, and all but 3 responded to vaccination. We conclude that immunoglobulin deficiencies and the inability to respond to polysaccharide antigens are common risk factors for recurrent pneumonia in adult patients. Immunoglobulin levels (including IgG subclasses) and antibody response to polysaccharide antigens should be investigated in these patients.

The association between an acquired form of hyper-IgM syndrome and a chronic hepatitis C virus (HCV) infection in a 71-year-old female patient is described. Both diseases were diagnosed at the age of 58 years. She was started on intramuscular and then intravenous immunoglobulin replacement therapy. HCV RNA was detected in 1992. The patient remained in well-balanced clinical condition until 1994, when total and specific anti-HCV IgM levels increased and the patient developed an IgM kappa monoclonal gammopathy. Adherent cells and B cells were HCV RNA positive, while T cells were HCV RNA negative. Anti-IgM reactivity was specifically directed to the core antigen of the HCV. The patient we describe showed a picture of a late-onset form of hypogammaglobulinemia with a progressive increase in IgM antibodies, possibly due to the concomitant HCV infection. It is possible that the immunodeficiency might also result from the HCV infection, with formation of specific antibodies belonging to the IgM class, and that the worsening of the clinical condition may be directly related to the persistent viral infection.

We report a case of selective IgM deficiency associated with systemic lupus erythematosus (SLE). A 34-year-old female suffering from SLE was admitted with proteinuria and general fatigue. Laboratory findings revealed a very low serum IgM level, almost lower than 12 mg/dl. Renal biopsy findings showed diffuse proliferative lupus nephritis (DPLN). In immunofluorescent microscopy, IgG was the most strongly stained followed by IgA, but IgM staining was only faint. As for the immunophenotype of the T cells, the OKT4/OKT8 ratio was normal. Response to both phytohemagglutinin (PHA) and concanavalin A (ConA) was normal. However, responses of B cells to both pokeweed mitogen (PWM) and Staphylococcus aureus Cowan strain I (SAC) were significantly reduced. Surface IgM-positive B cells were decreased. These results indicate that the patient had B cell dysfunction, involving impairment of B cell differentiation. In this report, we discuss selective IgM deficiency and SLE documented in the literature.

Introduction: Monoclonal light and heavy chain deposition disease is a rare syndrome distinct from light chain amyloid, which is defined by the presence of monoclonal deposits of immunoglobulins in various tissues., Case-Report: A 65-year-old man presented with renal symptoms due to membranoproliferative glomerulonephritis, associated with urticarial papules located on the arms and back. Histological examination of a skin biopsy specimen showed lymphocytic vasculitis. Direct immunofluorescence examination of kidney and skin lesions using anti-gamma 2 and anti-Kappa monoclonal antibodies, showed a similar staining on the basement membrane zone and vessel walls., Comments: As far as we know, this is the first documentation of monoclonal light and heavy chain deposition disease associated with a lymphocytic skin vasculitis and renal involvement caused by similar monoclonal deposits of immunoglobulins in the kidney and skin.

Monoclonal gammopathy, especially monoclonal gammopathy of undetermined significance (MGUS) with IgM M-components, are associated with demyelinating neuropathy. In approximately 50% of these patients, the IgM M-component reacts with myelin associated glycoprotein (MAG) or other subcomponents of myelin such as glycolipids or gangliosides and a pathogenetic role of the M component has been proposed. Polyneuropathies associated with monoclonal gammopathies are of interest because of the potential relationship between the monoclonal protein and immune-mediated nerve damage. Many patients have been described in whom polyneuropathy is associated with IgM or IgG monoclonal gammopathy. While some such patients have MGUS, others have a variety of malignant plasma cell dyscrasia. The associated polyneuropathies clinically, electrodiagnostically, and histologically heterogeneous, but some exhibit primarily demyelination features, while others show axonal features. I have reviewed clinical, and immunological data in patients with MGUS and polyneuropathy in our clinic. The mechanism of neuropathy in patients with monoclonal gammopathy in the field of immunological studies is also reviewed. In summary, antibody activity in patients with monoclonal gammopathies associated with peripheral neuropathies almost exclusively found in monoclonal proteins of the IgM class. The most prevalent antibody is directed against MAG. IgG and IgA monoclonal proteins did not react components of peripheral nerve myelin. IgM-MGUS neuropathy should be separated conceptionally from monoclonal IgG neuropathies from my data.

The clinical, laboratory and pathological findings are reported in an adolescent patient with hyper-IgM immunodeficiency syndrome (dysgammaglobulinemia) which was complicated by primary sclerosing cholangitis and membranous glomerulonephritis. Hepatitis C virus (HCV) RNA was detected in serum by the polymerase chain reaction. A possible etiological relationship between hepatitis C virus infection and membranous nephropathy is discussed.

Twenty-five patients with acute lymphoblastic leukaemia (ALL) aged 10 months to 43 years and twenty-five age and sex matched healthy control subjects were investigated in this study. Serum immunoglobulins A, G and M levels were measured by single radial immunodiffusion method and immune complex levels estimated by polyethylene glycol precipitation technique. Significant increase in immune complexes and decrease in immunoglobulin G were observed in the patients. Although not statistically significant, the patients had a lower mean level of immunoglobulin A, and a higher mean immunoglobulin M concentration than the controls. Hypoimmunoglubulinaemia observed in this study may contribute to the aetiology of ALL or be an effect of the disease. Raised immune complexes could result from specific antibodies combining with tumour associated or microbial antigens. Immunoglobulin G levels showed a significant positive correlation with survival in the patients. The adverse effect of reduced immunoglobulin G on the prognosis of ALL is probably due to compromised immunity in the patients.

Dysgammaglobulinemia, amyloidosis and generalization of tumour occurred step by step in sensomotoric polyneuropathy complicating a nonspecified malignant lymphoma. The tumor was specified later as a IgM lambda immunocytoma with substantial participation of signet ring cells. Their vacuoles were sometimes multivesicular and did not contain immunoglobulins. Final phase of the disease was characterized by nodular AL amyloidosis expressed especially in the lung, retroperitoneum and nervous system. Amyloidosis was connected with the vessel walls and their surroundings. Possible autoimmune pathogenesis of polyneuropathy as well as of immunocyte vacuolization were discussed.

In 36 patients with ischemic stroke the study of factors influencing the yield shear stress, which exemplified the red cells and fibrinogen interaction, was carried out. Patients were divided into two clinical groups: with transient ischemic attack (TIA) and with completed stroke (CS). The frequency of the intensive red cells and fibrinogen interaction was significantly higher in patients the in controls, which may be connected with dysgammaglobulinemia and with an increase of the red cell volume. The lack of significant difference between TIA and CS groups indicated the similar pathomechanism of blood flow changes in cerebral microcirculation in acute phase of TIA as well as of CS. It seems that individual hemorheological changes should be considered first of all in the therapy of this disease.

We reported two cases of anaphylactoid reaction caused by ranitidine and alprostadil. We suggest that these anaphylactoid reactions are nonspecific reactions which are observed in low IgE patients, because plasma IgE was still low 6 weeks after allergic reaction and these drugs have not been given to them before and eosinophilic and basophilic cells showed no change at all. We have to consider that there is a high risk of allergic reaction during general anesthesia, because many drugs are injected intravenously during general anesthesia.