Primary Hypogammaglobulinemia Research Articles

IgD+IgM- B Cells in Common Variable Immunodeficiency.

Common variable immunodeficiency (CVID) is the most frequent form of primary hypogammaglobulinemia in adults. In addition to recurrent infections and respiratory manifestations, CVID patients may present several non-infection complications such as autoimmune diseases. The mechanisms that lead to immune dysregulation in CVID are not completely understood. Given the role of IgD on naïve B cells in the maintenance of tolerance and secreted IgD in the respiratory mucosa, we evaluated the frequency of IgD+ naïve and IgD+ memory B cells in CVID patients. Here, no differences were observed in the percentages and proliferative responses of anergic IgD+IgM-CD27- B cells between CVID patients, with or without autoimmune disease, and the control group. Interestingly, in the compartment of memory B cells, the percentage of IgD+IgM- cells was higher only in CVID patients with allergic rhinitis/allergic asthma. Our results may indicate that anergic IgD+IgM-CD27- B cells may not be compromised in our CVID cohort. However, IgD+IgM- memory B cells may play a role in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients. Further studies are needed to better understand the participation of IgD+IgM- memory B cells in the immunopathogenesis of allergic rhinitis/allergic asthma in CVID patients.

T cell immunity following COVID-19 vaccination in adult patients with primary antibody deficiency - a 22-month follow-up.

Primary antibody deficiencies, such as common variable immunodeficiency (CVID), are heterogenous disease entities consisting of primary hypogammaglobulinemia and impaired antibody responses to vaccination and natural infection. CVID is the most common primary immunodeficiency in adults, presenting with recurrent bacterial infections, enteropathy, autoimmune disorders, interstitial lung diseases and increased risk of malignancies. Patients with CVID are recommended to be vaccinated against SARS-CoV-2, but there are relatively few studies investigating humoral and cellular responses to immunization. We studied the dynamics of humoral and cell-mediated immunity responses up to 22 months in 28 patients with primary immunodeficiency and three patients with secondary immunodeficiency receiving ChAdOx1, BNT162b2 and mRNA-1273 COVID-19 vaccines. Despite inadequate humoral response to immunization, we demonstrate a robust T cell activation likely protecting from severe COVID-19.

The Rapidly Expanding Genetic Spectrum of Common Variable Immunodeficiency–Like Disorders

The understanding of common variable immunodeficiency disorders (CVID) is in evolution. CVID was previously a diagnosis of exclusion. New diagnostic criteria have allowed the disorder to be identified with greater precision. With the advent of next-generation sequencing (NGS), it has become apparent that an increasing number of patients with a CVID phenotype have a causative genetic variant. If a pathogenic variant is identified, these patients are removed from the overarching diagnosis of CVID and are deemed to have a CVID-like disorder. In populations where consanguinity is more prevalent, the majority of patients with severe primary hypogammaglobulinemia will have an underlying inborn error of immunity, usually an early-onset autosomal recessive disorder. In nonconsanguineous societies, pathogenic variants are identified in approximately 20% to 30% of patients. These are often autosomal dominant mutations with variable penetrance and expressivity. To add to the complexity of CVID and CVID-like disorders, some genetic variants such as those in TNFSF13B (transmembrane activator calcium modulator cyclophilin ligand interactor) predispose to, or enhance, disease severity. These variants are not causative but can have epistatic (synergistic) interactions with more deleterious mutations to worsen disease severity. This review is a description of the current understanding of genes associated with CVID and CVID-like disorders. This information will assist clinicians in interpreting NGS reports when investigating the genetic basis of disease in patients with a CVID phenotype.

Hepatitis E infection in adults with primary immunodeficiency with or without immunoglobulin replacement therapy.

In a context of secondary immunodeficiency, hepatitis E virus (HEV) infection can be responsible for chronic liver disease. We investigated HEV infection in patients with primary immunodeficiency treated (or not) with immunoglobulin (Ig) replacement therapy (IgRT) in France, a country with a high seroprevalence of HEV. In a nationwide study of individuals with primary immunodeficiency, 533 patients (349 and 184 receiving IgRT or not, respectively) were tested for HEV RNA and anti-HEV antibodies. In addition, 23 batches of five different commercially available immunoglobulin preparations were screened for anti-HEV IgG. Three of the 533 patients displayed markers of a recent HEV infection (HEV RNA in one case, and anti-HEV IgG and IgM in two) but no evidence of chronic liver disease. The overall seroprevalence of HEV was 50% (266 out of 533), with values of 68% and 16% in patients receiving IgRT or not, respectively (p<0.001). Anti-HEV IgG were detected in all batches of immunoglobulin preparations, although the titer varied from 3 to 127 IU/g IgG. Seroconversion was observed in 15 of the 22 (68%) patients tested before and after IgRT. No cases of chronic HEV-related disease were detected among patients with primary immunodeficiency and hypogammaglobulinemia, whether they received IgRT or not. This confirms that patients with primary immunodeficiency have a low risk of chronic infection despite a seroprevalence close to that observed in the French general population and that IgRT, which confers a high HEV seroprevalence, might play a key role in protection against chronic infection.

HYPOGAMMAGLOBULINEMIA AS A PRESENTING FINDING OF DGAT1 DEFICIENCY

<h3>Introduction</h3> The constellation of failure to thrive, chronic intractable diarrhea, and hypogammaglobulinemia should prompt the clinician to consider inborn errors of immunity (IEI), including defects in cellular and humoral immunity, immune dysregulatory disorders, and autoinflammatory disorders. However, the differential diagnosis should remain broad to include secondary causes of hypogammaglobulinemia, such as congenital diarrhea and enteropathies (CODEs). <h3>Case Description</h3> A two-week-old, full-term male presented with persistent diarrhea and failure to thrive. Endoscopic evaluation of the bowel showed active duodenitis and active colitis. Food protein-induced enterocolitis syndrome (FPIES) was considered due to transient improvement in stool output on an elemental formula; however, diarrhea recurred after advancing enteral feeds. Newborn screen was normal. Laboratory evaluation showed normal lymphocyte subpopulations, hypogammaglobulinemia (IgG < 108 mg/dL with normal IgA, IgM, IgE), hypoalbuminemia, and an elevated stool alpha-1 antitrypsin. Genetic testing revealed a compound heterozygous mutation in DGAT1 (c.1183C>T, c.329+6T>G). He received two doses of intravenous immunoglobulin; however, the stool output and IgG level resolved after starting a low-fat elemental formula. The patient remains on a low-fat diet with normal growth parameters and no recurrent infections with a normal IgG level. <h3>Discussion</h3> DGAT1 (diacylglycerol acyltransferase 1) deficiency is a protein-losing enteropathy due to defective lipid metabolism that is treated with a low-fat diet. Protein-losing conditions can cause hypoalbuminemia and hypogammaglobulinemia due to enteral loss of plasma proteins. It is important for clinicians to consider both primary hypogammaglobulinemia due to IEI and other conditions associated with secondary hypogammaglobulinemia when evaluating a patient with hypogammaglobulinemia.

Lymphoma as an Exclusion Criteria for CVID Diagnosis Revisited.

Hypogammaglobulinemia in a context of lymphoma is usually considered as secondary and prior lymphoma remains an exclusion criterion for a common variable immunodeficiency (CVID) diagnosis. We hypothesized that lymphoma could be the revealing symptom of an underlying primary immunodeficiency (PID), challenging the distinction between primary and secondary hypogammaglobulinemia. Within a French cohort of adult patients with hypogammaglobulinemia, patients who developed a lymphoma either during follow-up or before the diagnosis of hypogammaglobulinemia were identified. These two chronology groups were then compared. For patients without previous genetic diagnosis, a targeted next-generation sequencing of 300 PID-associated genes was performed. A total of forty-seven patients had developed 54 distinct lymphomas: non-Hodgkin B cell lymphoma (67%), Hodgkin lymphoma (26%), and T cell lymphoma (7%). In 25 patients, lymphoma developed prior to the diagnosis of hypogammaglobulinemia. In this group of patients, Hodgkin lymphoma was overrepresented compared to the group of patients in whom lymphoma occurred during follow-up (48% versus 9%), whereas MALT lymphoma was absent (0 versus 32%). Despite the histopathological differences, both groups presented with similar characteristics in terms of age at hypogammaglobulinemia diagnosis, consanguinity rate, or severe T cell defect. Overall, genetic analyses identified a molecular diagnosis in 10/47 patients (21%), distributed in both groups and without peculiar gene recurrence. Most of these patients presented with a late onset combined immunodeficiency (LOCID) phenotype. Prior or concomitant lymphoma should not be used as an exclusion criteria for CVID diagnosis, and these patients should be investigated accordingly.

Genetic Diagnosis Guides Treatment of Autoimmune Enteropathy

Autoimmune enteropathy (AIE) is a severe form of enteropathy characterized by chronic diarrhea refractory to any exclusion diet and associated with autoimmunity.1,2 Despite this clear definition, diagnosis is challenging. The presence of antienterocyte antibodies against the AIE-75kDa antigen3 is a strong but inconstant biomarker. In a recent cohort of 40 AIE patients, antienterocyte antibodies were reported in only 14% (4/28) of the cases, likely caused by the high frequency of patients with primary hypogammaglobulinemia.

Hypogammaglobulinemia and Multiple Sclerosis - An Overlooked Correlation?

Hypogammaglobulinemia and Multiple Sclerosis - An Overlooked Correlation? Abstract. Hypogammaglobulinemias occur in people with multiple sclerosis (MS) without immunotherapy in 8.1% of patients and with immunotherapy (not drug-specific) in up to 26.4% of affected individuals. This is thus significantly higher than the expected incidence in the general population. In MS patients it is also relevant to differentiate between primary and secondary hypogammaglobulinemia. In particular, anti-CD20 therapies are mainly underlying for the secondary forms in MS patients. With this article, we aim to provide a "spotlight" on hypogammaglobulinemia with a focus on the clinical consequence of these phenomena in people with MS.

Intravenous immunoglobulin therapy for COVID-19 ARDS

Intravenous immunoglobulin therapy for COVID-19 ARDS

Primary Hypogammaglobulinaemia with Inflammatory Bowel Disease-Like Features: An ECCO CONFER Multicentre Case Series.

Hypogammaglobulinaemia is a disorder characterized by low serum immunoglobulin levels and a high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease [IBD]. This was a multicentre case series performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. This report includes 27 patients with primary hypogammaglobulinaemia and IBD-like features: 20 males and seven females, median age 45.6 years (interquartile range [IQR] 35.2-59). Crohn's disease-like features were noted in 23 patients, and four patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinaemia preceded a diagnosis of IBD-like features in 20 patients [median of 7 years prior, IQR 2.6-20.6 years], and followed the appearance of IBD-like features in seven cases [median of 1 year after, IQR 0.45-5.6 years]. Hypogammaglobulinaemia aetiologies were common variable immunodeficiency [66.6%], agammaglobulinaemia [7.4%], selective IgA-deficiency [11.1%], Good's syndrome [7.4%], IgG subclass deficiency with IgA deficiency [3.7%] and hyper-IgM [3.7%]. In addition to antibiotics and intravenous immunoglobulin [IVIG] for hypogammaglobulinaemia, 12 patients received IBD-related treatment including 5-aminosalicylate agents [two patients], corticosteroids [one patient], thiopurines [three patients], anti-tumour necrosis factor [four patients] and vedolizumab [two patients]. By the end of the follow-up (44.5 months [IQR 18-81]), 21/27 [77%] patients were in clinical remission. This case series describes IBD-like features in patients with hypogammaglobulinaemia. The diagnosis of IBD-like features mainly occurred after that of hypogammaglobulinaemia, with successful recovery in the majority of cases after appropriate treatment.

DOP79 Primary hypogammaglobulinemia with IBD-like features: An ECCO CONFER Multicenter Case Series

Abstract Background The most commonly recognized clinical feature of hypogammaglobulinemia is recurrent infections with high prevalence of gastrointestinal manifestations. In some cases, clinical and endoscopic features are indistinguishable from those of inflammatory bowel disease (IBD). Methods This was a multicenter case series performed as a part of the Collaborative Network of Exceptionally Rare case reports (CONFER) project. Results This report includes 25 patients with primary hypogammaglobinemia and IBD-like features [20 males and 5 females, mean age 50 years (±21.7 SD)]. Crohn’s disease-like features were noted in 22 patients, three patients had ulcerative colitis-like features. The diagnosis of hypogammaglobulinemia preceded IBD-like features diagnosis in 20 patients (mean of 7.7 years prior, range 0.3–35 years), and followed IBD-like features appearance in 5 cases (mean of one year after, 0.4- 9.1 years). Hypogammaglobinemia etiologies were common variable immunodeficiency (72%), Agammaglobulinemia (8%), selective IgA-deficiency (8%), Goods syndrome (8%), IgG subclass deficiency with IgA deficiency (4%). In addition to antibiotics and intravenous immunoglobulin (IVIG) as a treatment for hypogammaglobinemia, fifteen patients received IBD treatment during the follow-up period, of whom two were on 5-aminosalicylic acid, five on corticosteroids, three on immunomodulatory, four on anti-tumor necrosis factor, and one on vedolizumab. By the end of the follow-up [35.5 months (Interquartile range 18–75)], 20 of 25 (80%) patients were in clinical remission. Conclusion This case series illustrates a strong male and CD-like features predilection. The diagnosis of IBD-like features mainly occurs after that of hypogammaglobulinemia, the majority of cases successfully recovered after appropriate treatment.

High frequency of variants in genes associated with primary immunodeficiencies in patients with rheumatic diseases with secondary hypogammaglobulinaemia

ObjectivesTreatment of rheumatic diseases requires immunomodulatory agents which can compromise antibody production. However, even in case of agents directly targeting B cells, a minority of patients develop hypogammaglobulinaemia, suggesting a...

Comparison of Oral Findings of Common Variable Immune Deficiency and Nephrotic Syndrome Patients with Hypogammaglobulinemia to Healthy Individuals

A group of disorders featuring lower serum immunoglobulin levels is called hypogammaglobulinemia. Being a primary immune disorder, Common variable immunodeficiency (CVID) is characterized by primary hypogammaglobulinemia. Nephrotic syndrome (NS) is an entity associated with secondary hypogammaglobulinemia. Lower concentrations of immunoglobulins in saliva may attenuate oral health. The aim of this study is to investigate the impact of salivary immunoglobulin concentrations on oral health in patients with primary and secondary hypogammaglobulinemia.

Peripheral Blood Lymphocyte Phenotype Differentiates Secondary Antibody Deficiency in Rheumatic Disease from Primary Antibody Deficiency.

The phenotype of primary immunodeficiency disorders (PID), and especially common variable immunodeficiency (CVID), may be dominated by symptoms of autoimmune disorders. Furthermore, autoimmunity may be the first manifestation of PID, frequently preceding infections and the diagnosis of hypogammaglobulinemia, which occurs later on. In this case, distinguishing PID from hypogammaglobulinemia secondary to anti-inflammatory treatment of autoimmunity may become challenging. The aim of this study was to evaluate the diagnostic accuracy of peripheral blood lymphocyte phenotyping in resolving the diagnostic dilemma between primary and secondary hypogammaglobulinemia. Comparison of B and T cell subsets from patients with PID and patients with rheumatic disease, who developed hypogammaglobulinemia as a consequence of anti-inflammatory regimes, revealed significant differences in proportion of naïve B cells, class-switched memory B cells and CD21low B cells among B cells as well as in CD4+ memory T cells and CD4+ T follicular cells among CD4+ T cells. Identified differences in B cell and T cell subsets, and especially in the proportion of class-switched memory B cells and CD4+ T follicular cells, display a considerable diagnostic efficacy in distinguishing PID from secondary hypogammaglobulinemia due to anti-inflammatory regimens for rheumatic disease.

Recurrent Campylobacter Enteritis in Patients with Hypogammaglobulinemia: Review of the Literature.

Recurrent Campylobacter enteritis is a well-recorded complication of primary hypogammaglobulinemia but has only rarely been reported with other types of immunodeficiency, and no cases have been reported after rituximab-associated secondary hypogammaglobulinemia. We therefore reviewed our local microbiology laboratory databases and conducted a literature search, to provide a detailed characterization of the immunodeficiency states associated with recurrent Campylobacter enteritis. Published cases had primary hypogammaglobulinemia, most frequently in the setting of common variable immunodeficiency, x-linked agammaglobulinemia, and Good syndrome. No cases were identified in the literature after rituximab or secondary hypogammaglobulinemia. We report a 73-year-old patient with recurrent Campylobacter enteritis and hypogammaglobulinemia in the setting of non-Hodgkin lymphoma, chemotherapy, and maintenance rituximab. Physicians should be aware of the association of recurrent Campylobacter enteritis and immunodeficiency, most commonly in primary hypogammaglobulinemia. Rituximab alone may not be sufficiently immunosuppressive for recurrent campylobacteriosis to occur; additional factors, including hematological malignancy and its treatment, appear necessary. Patients with recurrent Campylobacter enteritis and those starting rituximab should be investigated for hypogammaglobulinemia and B-lymphopenia.

All Patients With Common Variable Immunodeficiency Disorders (CVID) Should Be Routinely Offered Diagnostic Genetic Testing.

Common Variable Immunodeficiency Disorders (CVID) are a rare group of primary immunodeficiency disorders (PIDs) where late onset antibody failure leads to immune system failure (1). Onset of symptoms can occur from early childhood to the eighth decade or later (2). Current estimates suggest a prevalence between 1: 25 000 to 1: 100 000 in Caucasians (3, 4). For reasons that are unclear, CVID appears to be less frequent in Asian and African populations, although there may be ascertainment bias. The majority of patients with CVID present with recurrent and severe infections. Untreated, patients are predisposed to chronic suppuration of the respiratory tract, often resulting in chronic sinus disease and bronchiectasis. Approximately 25% of CVID patients suffer autoimmune or inflammatory sequelae, consequent to immune dysregulation (5). There is also an increased risk of malignancy (6). There is no single clinical feature or laboratory test, which is pathognomonic for CVID. The identification of CVID therefore relies on diagnostic criteria. There are currently three new sets of diagnostic criteria for CVID (7–9). The Ameratunga et al. (7) criteria require symptomatic primary hypogammaglobulinemia with relevant laboratory tests to establish the diagnosis. The threshold for IgG was set at 5 g/l for adults. The revised European Society for immunodeficiencies (8) are similar to the Ameratunga et al. criteria. The most recent International Consensus Document (9) CVID criteria claim to be able to make a definite diagnosis on the basis of a single abnormal vaccine challenge result in a patient with primary hypogammaglobulinemia (9). The latter two criteria have set the threshold for IgG at 2 sd below the mean. Although immunoglobulin levels do not follow a Gaussian distribution (10), this is generally accepted as an IgG below 7 g/l. These criteria also exclude late onset combined immunodeficiency (LOCID) from the diagnosis. The immunoglobulin levels are also required to be repeated in these latter criteria. There is ongoing debate about the utility these diagnostic criteria, the variability of IgG levels over time, the unreliability of vaccine challenge responses and flow cytometry in the diagnosis of CVID. As discussed below, this variability in protein-based assays is a strong argument for genetic testing of all patients with a CVID phenotype.

Progressive Multifocal Leukoencephalopathy in a Patient with Multiple Myeloma Receiving Daratumumab and Pomalidomide

Background Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by reactivation of the polyomavirus John Cunningham (JCV) in the setting of immunosuppression. It has been described in patients with hematologic malignancies including multiple myeloma (MM), solid organ malignancies, granulomatous and inflammatory diseases, transplant recipients, lymphopenic patients (including patients with HIV) and with the use of certain drugs (rituximab, natalizumab). We present the first report to our knowledge of a patient with MM developing PML in association with daratumumab and pomalidomide therapy. Case Report A 63yo woman with relapsed/refractory IgA-Lambda MM on daratumumab and pomalidomide, presented to the emergency department after noticing difficulty putting her hair up in a ponytail. Her MM was diagnosed in 2003 and treated with steroids, high-dose melphalan and autologous stem cell transplant, maintenance therapy with thalidomide, switched to lenalidomide; upon relapse in 2010, she was treated with bortezomib, doxorubicin and dexamethasone, followed by bortezomib maintenance. Ten months prior to presentation, she relapsed and was started on daratumumab and pomalidomide, achieving an unconfirmed complete response (uCR), complicated by acquired hypogammaglobulinemia for the prior 8 months without infections. She developed progressive left arm weakness and gait instability; she denied any fevers, dysarthria, vision changes, headaches or seizures. On exam, she was alert and oriented; no cranial nerve abnormality; calculation, concentration and recall were intact; 4/5 strength in left upper extremity and 5/5 strength in all other extremities with preserved sensation and reflexes; coordination intact but a hemiparetic gait; rest of the exam was unremarkable. A brain MRI showed patchy and confluent areas of T2 hyperintense signal in the right greater than left cerebral hemispheres. She underwent a lumbar puncture which was positive for JCV by PCR (98 copies/mL) in her CSF and negative for neoplastic involvement by flow cytometry. The rest of her work-up was unremarkable. A diagnosis of PML was made and daratumumab and pomalidomide were discontinued. On follow-up brain MRIs four and eight weeks later, she had persistent extensive asymmetric patchy T2 hyperintense signal. Repeat LP revealed stable JCV in the CSF (95 copies/mL). Despite the lack of radiologic improvement, she had a remarkable clinical response with near resolution of neurologic symptoms and remains in an uCR. Discussion PML has been reported in association with multiple drugs used in the management of MM including corticosteroids, alkylating agents (cyclophosphamide, melphalan), immunomodulatory drugs (thalidomide, lenalidomide) and proteasome inhibitors (bortezomib, ixazomib), however, an association with pomalidomide or daratumumab has not yet been reported. In a clinical trial of daratumumab and pomalidomide for MM, a case of PML was reported, however, it was not considered to be related to these agents given that the patient received only one dose of daratumumab (Chari A. Blood 2017). PML has been reported in patients with primary hypogammaglobulinemia, however, it is not known whether acquired hypogammaglobulinemia - either due to MM or its therapy - is a risk factor for PML. Furthermore, the role for IVIG in the primary prevention or treatment of PML has not been clearly defined and warrants further study. The current treatment approach of PML remains the restoration of the host's adaptive immune response, including the discontinuation of immunosuppressive agents, unfortunately, evidence is lacking for any specific pharmacologic treatment. Recently, immune checkpoint inhibitors have shown clinical improvement or stabilization in small cohorts of patients with PML (NEJM 2019;380), however, given the safety concerns regarding their use in MM (KEYNOTE-183,-185) and the rapid clinical response seen in this case, no further therapy was instituted. This is the first report of pomalidomide and daratumumab as potential drugs associated with PML. Although it is not possible to ascertain their direct role in the reactivation of JCV, it should help clinicians recognize this potentially fatal complication in patients receiving either immunomodulatory drugs or anti-CD38 monoclonal antibodies, since prompt discontinuation may be life-saving. Disclosures Perry: Celgene: Speakers Bureau. Coleman:Gilead, Bayer, Celgene: Consultancy, Research Funding, Speakers Bureau; Kite Pharmaceuticals: Equity Ownership; Merck: Research Funding; Pharmacyclics: Speakers Bureau. Rossi:Janssen, Celgene, Amgen: Consultancy; BMS: Research Funding. Niesvizky:Takeda, Amgen, BMS, Janssen, Celgene: Consultancy, Research Funding.

CLINICAL ANALYSIS OF THE COMMON VARIABLE IMMUNODEFICIENCY IN PATIENTS WITH LUNG DISEASES: EXPERIENCE IN JAPAN

SESSION TITLE: Monday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Common variable immunodeficiency (CVID) is a heterogeneous subset of primary immunodeficiencies, which is characterized by hypogammaglobulinemia, defective antibody production and increased susceptibility to infection. Clinically, recurrent respiratory infections are a significant problem because those might lead to bronchiectasis, declining in lung function, and impairment of their quality of life. It is reported that over 90% of CVID patients suffer from the upper and lower respiratory tract infections due to increased susceptibility to bacterial pathogens. The purpose of this study is to assess clinical characteristics of CVID in our patients with lung diseases and to reveal the relationship between CVID and respiratory infections, especially lower respiratory tract infections. METHODS: From April 2016 to September 2018, consecutive 3417 patients with lung diseases, whose serum immunoglobulin were measured, were retrospectively studied. Among those cases, 451 patients with hypogammaglobulinemia were detected, and 336 patients were diagnosed with primary hypogammaglobulinemia, and 112 were secondary as a result of medications with corticosteroids or immunosuppressant, and so on. Of 336 patients with primary hypogammaglobulinemia, 37 patients were clinically diagnosed with CVID. Clinical features and lower respiratory infection frequency of those cases were analyzed retrospectively. RESULTS: Anong total of 37 patients with CVID, 7 cases showed low levels of IgG, IgA, and IgM (Gr. A), 10 did low levels of IgG and IgA (Gr. B), 20 did low levels of IgG and IgM (Gr. C), and 2 did low levels of IgA and IgM (Gr. D). Depending upon each Gr., 6 cases (85.7%), 6 (60%), 9 (45%), and 0 (0%) had any previous histories of lower respiratory infections, respectively. In addition, 4 (66.6%), 3 (50%), 1 (11%), 0 (0%) of each Gr. experienced recurrent infections. Bacteriologically, Klebsiella spp. (7), Pseudomonas spp. (5) and Haemophilus influenzae (4) were the three most common bacterial pathogens detected in respiratory samples (sputum, bronchial washings) from CVID patients. Radiologically, bronchiectasis (19) and nodular shadows (12) were often detected in Chest CT among those patients with CVID. CONCLUSIONS: The present study revealed that lower respiratory infections occurred in CVID patients with high frequency, and that majority of them suffered from recurrent infections, which might lead to bronchiectasis and bacterial colonization of the respiratory tract. Especially, low immunoglobulin levels of IgG, IgA, and IgM were at high risk for infections. CLINICAL IMPLICATIONS: Clinicians should take into consideration the possibility of CVID when a patient suffers from recurrent infections and show hypogammaglobulinemia. DISCLOSURES: No relevant relationships by NAOKI ARAI, source=Web Response No relevant relationships by Hitomi Goto, source=Web Response No relevant relationships by Kenji Hayashihara, source=Web Response No relevant relationships by Kentaro Hyodo, source=Web Response No relevant relationships by Yuka Kitaoka, source=Web Response No relevant relationships by Sosuke Matsumura, source=Web Response No relevant relationships by Yukiko Miura, source=Web Response No relevant relationships by Mizu Nonaka, source=Web Response No relevant relationships by SHUJI OH-ISHI, source=Web Response No relevant relationships by Takefumi Saito, source=Web Response No relevant relationships Added 03/12/2019 by Yuika Sasatani, source=Web Response, value=Salary Removed 03/12/2019 by Yuika Sasatani, source=Web Response No relevant relationships by TAKAFUMI SHIMADA, source=Web Response No relevant relationships by YUKI TAKAGI, source=Web Response

Особливості ведення дітей із первинними та вторинними гіпогаммаглобулінеміями (огляд літератури)

Особливості ведення дітей із первинними та вторинними гіпогаммаглобулінеміями (огляд літератури)

Reconstitution of IgG Subclasses following Immunoglobulin Therapy in Adult Primary Hypogammaglobulinemia

Background: Immunoglobulin (Ig) therapy is highly effective in reducing the frequency and severity of infections. However, a subset of patients does not respond adequately. Objective: To determine in adult patients with primary hypogammaglobulinemia (a) if failure to reconstitute IgG subclass(es) is associated with inadequate clinical response, (b) whether reconstitution of IgG subclasses differs between routes of Ig administration, (c) which subclasses contribute to low total IgG, and (d) what are the most commonly impaired Streptococcus pneumoniae serotypes. Methods: A retrospective review of the records of patients with primary hypogammaglobulinemia followed up at the Immunology Clinic between 2010 and 2018 was conducted. Demographic, clinical, and laboratory data were collected. Results: Seventy-one patients with primary hypogammaglobulinemia were included. All subclasses were reconstituted in 85% of the patients. IgG3 and IgG4 were most commonly not reconstituted. Reconstitution occurred in 85% of the patients on intravenous Ig (IVIG), 81% of the patients on conventional subcutaneous Ig (SCIG), and 100% of the patients on enzyme-facilitated subcutaneous Ig (fSCIG). The annual infection rate was 0.87 with IVIG, 0.88 with conventional SCIG, and 0.6 with fSCIG. IgG subclasses contributing to low total IgG included IgG1 (61%), IgG2 (49%), IgG3 (23%), and IgG4 (28%). In patients with concomitant specific antibody deficiency (n = 47), the most commonly impaired antibody responses were against pneumococcal serotypes 3, 4, 6b, 12f, and 23f. Conclusions: Failure to reconstitute subclasses does not correlate with an inadequate clinical response to immunoglobulin therapy in primary hypogammaglobulinemia. Full reconstitution of IgG subclasses was observed with fSCIG. A smaller panel of pneumococcal antibody responses may be used to define specific antibody deficiency.