INTRODUCTION: The impact of chemoimmunotherapy (CIT) on immunoglobulin (Ig) quantities in patients with chronic lymphocytic leukemia (CLL) has not been extensively studied. METHODS: We analyzed Ig levels in 45 stable patients with indolent CLL (without indication for treatment) and 87 patients with progressive disease before first-line treatment. Fifty-five patients were evaluated again after the treatment with CIT. RESULTS: We observed significantly lower levels of all Ig classes and subclasses in patients with progressive disease compared to patients with indolent disease. After treatment, median IgA increased from 0.59 g/L to 0.74 g/L (p = 0.0031). In stable patients, lower IgA2 was associated with shorter time to first treatment, although it did not reach statistical significance (p = 0.056). Shorter overall survival was observed in patients with progressive disease and lower IgG2 (p = 0.043). Surprisingly, among the patients with progressive CLL, unmutated IGHV genes were associated with higher levels of IgG, IgG1 and IgM, while TP53 mutation and/or 17p deletion were associated with higher levels of IgA and IgA1. CONCLUSIONS: CIT may lead to increase in IgA levels. Hypogammaglobulinemia is more common in patients with progressive CLL and unmutated IGHV or TP53 dysfunction.

• MeSH
• Leukemia, Lymphocytic, Chronic, B-Cell * drug therapy   blood   immunology   mortality   MeSH
• Adult MeSH
• Immunoglobulin A * blood   MeSH
• Immunotherapy methods   MeSH
• Middle Aged MeSH
• Humans MeSH
• Disease Progression MeSH
• Antineoplastic Combined Chemotherapy Protocols therapeutic use   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

The elastase, which belongs to the serine protease family, hydrolyses various proteins and may be involved in the parasite invasion. In this study, complete sequence of elastase-1 (TsE) the nematode Trichinella spiralis (Owen, 1835) was cloned into the plasmid pcDNA3.1 as TsE DNA vaccine. After intramuscular vaccination, serum anti-Trichinella antibodies (IgG and subclass IgG1/IgG2a, and IgA), total and specific intestinal mucosal sIgA in mice vaccinated with pcDNA3.1/TsE were measured by ELISA. The results showed that vaccination with pcDNA3.1/TsE induced a systemic humoral immune response (high levels of serum IgG and subclass IgG1/IgG2a and IgA) and local intestinal mucosal immune responses (high levels of TsE-specific sIgA). Vaccination of mice with TsE DNA vaccine also triggered a systemic and local concomitant Th1/Th2 response, as demonstrated by significant elevation of Th1 (IFN-γ and IL-2) / Th2 (IL-4 and IL-10) cytokine levels after the spleen, mesenteric lymph node and Peyer's patch cells from vaccinated mice were stimulated with recombinant TsE (rTsE). The vaccination of mice with pcDNA3.1/TsE displayed a 17% reduction of intestinal adult worms and a 39% reduction of muscle larvae. Our results indicated that TsE DNA vaccine elicited a systemic concomitant Th1/Th2 response and an enteral local sIgA response, and produced a partial protection against infection with T. spiralis. The TsE may be regarded as a potential candidate vaccine target against Trichinella infection. The oral polyvalent vaccines should be developed to improve the protective efficacy of anti-Trichinella vaccines.

• MeSH
• Vaccines, DNA * administration & dosage   MeSH
• Mice MeSH
• Pancreatic Elastase * administration & dosage   pharmacology   immunology   MeSH
• Helminth Proteins * administration & dosage   pharmacology   immunology   MeSH
• Trichinella spiralis * immunology   MeSH
• Trichinellosis * immunology   parasitology   MeSH
• Vaccination * MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The clinical value of assessing immunoglobulin (Ig)G and IgA subclasses in addition to the isotypes of soluble Igs in serum has been well established. >20years ago, the International Union of Immunological Societies and the World Health Organization performed collaborative studies in order to validate antibody (Ab) clones for the detection of IgG and IgA subclasses for a broad range of laboratory assays, except for flow cytometry. Here we analyzed the performance of commercially available Ab clones to detect IgG and IgA subclasses in memory B-cells and plasma cells (PCs) by flow cytometry. In a first step, 28 Ab clones were evaluated in peripheral blood from healthy donors. Only 17/28 clones showed reactivity against IgG and IgA subclasses expressed on the B-cell and PC surface membrane, including Ab clones for IgG1 (SAG1, HP6188, HP6001 and HP6186), IgG2 (SAG2, HP6014 and HP6002), IgG3 (SAG3, HP6095 and HP6050), IgG4 (SAG4), IgA1 (SAA1, H69-11.4 and B3506B4) and IgA2 (SAA2, 2E2, and A9604D2). In a second step, for each Ig subclass a single clone was selected according to its specificity and fluorescence intensity (resolution power), for further more detailed validation (SAG1, SAG2, SAG3, SAG4, SAA1 and SAA2). This validation process was carried out in 4 different laboratories by testing the selected Ab clones in human peripheral blood, bone marrow and tonsil samples, using different staining protocols (e.g. surface membrane and/or cytoplasmic staining). All selected Ab clones displayed strong positivity, high specificity and optimal resolution between negative and positive cells. Alternative Ab clones were also validated. Thus, our results show the feasibility of using the validated Ig subclass Ab clones in combination with other B cell-associated markers for detailed dissection of the memory B-cell and PC compartments that express distinct Ig subclasses in different human tissues.

• MeSH
• B-Lymphocytes immunology   MeSH
• Adult MeSH
• Immunophenotyping methods   MeSH
• Immunoglobulin A analysis   MeSH
• Immunoglobulin G analysis   MeSH
• Middle Aged MeSH
• Humans MeSH
• Antibodies, Monoclonal * MeSH
• Plasma Cells immunology   MeSH
• Child, Preschool MeSH
• Flow Cytometry methods   standards   MeSH
• Aged MeSH
• Antibody Specificity * MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Validation Study MeSH

The cytopoxic effect of RL2 lactaptin (the recombinant analog of proteolytic fragment of human kappa-casein) toward tumor cells in vitro and in vivo presents it as a novel promising antitumor drug. The binding of any drug with serum proteins can affect their activity, distribution, rate of excretion and toxicity in the human body. Here, we studied the ability of RL2 to bind to various blood serum proteins. Using magnetic microparticles bearing by RL2 as an affinity matrix, in combination with mass spectrometry and western blot analysis, we found a number of blood serum proteins possessing affinity for RL2. Among them IgA, IgM and IgG subclasses of immunoglobulins, apolipoprotein A1 and various cortactin isoforms were identified. This data suggests that in the bloodstream RL2 lactaptin takes part in complicate protein-protein interactions, which can affect its activity.

• MeSH
• Chromatography, Affinity methods   MeSH
• Caseins metabolism   MeSH
• Blood Proteins analysis   isolation & purification   metabolism   MeSH
• Polymethacrylic Acids chemistry   MeSH
• Humans MeSH
• Magnets chemistry   MeSH
• Microspheres MeSH
• Antineoplastic Agents metabolism   MeSH
• Recombinant Proteins metabolism   MeSH
• Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization methods   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Predominantly antibody deficiencies (PADs) are the most prevalent primary immunodeficiencies, but their B-cell defects and underlying genetic alterations remain largely unknown. OBJECTIVE: We investigated patients with PADs for the distribution of 41 blood B-cell and plasma cell (PC) subsets, including subsets defined by expression of distinct immunoglobulin heavy chain subclasses. METHODS: Blood samples from 139 patients with PADs, 61 patients with common variable immunodeficiency (CVID), 68 patients with selective IgA deficiency (IgAdef), 10 patients with IgG subclass deficiency with IgA deficiency, and 223 age-matched control subjects were studied by using flow cytometry with EuroFlow immunoglobulin isotype staining. Patients were classified according to their B-cell and PC immune profile, and the obtained patient clusters were correlated with clinical manifestations of PADs. RESULTS: Decreased counts of blood PCs, memory B cells (MBCs), or both expressing distinct IgA and IgG subclasses were identified in all patients with PADs. In patients with IgAdef, B-cell defects were mainly restricted to surface membrane (sm)IgA+ PCs and MBCs, with 2 clear subgroups showing strongly decreased numbers of smIgA+ PCs with mild versus severe smIgA+ MBC defects and higher frequencies of nonrespiratory tract infections, autoimmunity, and affected family members. Patients with IgG subclass deficiency with IgA deficiency and those with CVID showed defects in both smIgA+ and smIgG+ MBCs and PCs. Reduced numbers of switched PCs were systematically found in patients with CVID (absent in 98%), with 6 different defective MBC (and clinical) profiles: (1) profound decrease in MBC numbers; (2) defective CD27+ MBCs with almost normal IgG3+ MBCs; (3) absence of switched MBCs; and (4) presence of both unswitched and switched MBCs without and; (5) with IgG2+ MBCs; and (6) with IgA1+ MBCs. CONCLUSION: Distinct PAD defective B-cell patterns were identified that are associated with unique clinical profiles.

• MeSH
• Child MeSH
• Adult MeSH
• Immunoglobulins deficiency   immunology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Plasma Cells immunology   MeSH
• Cell Count MeSH
• B-Lymphocyte Subsets immunology   MeSH
• Child, Preschool MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Immunologic Deficiency Syndromes immunology   MeSH
• Check Tag
• Child MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Child, Preschool MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

The goal of this work was to elucidate similarities between microorganisms from the perspective of the humoral immune system reactivity in professional athletes. The reactivity of serum IgG of 14 young, individuals was analyzed to 23 selected microorganisms as antigens by use of the in house ELISA. Serum IgM and IgA reactivity was also analyzed and a control group of sex and age matched individuals was used for comparison. The obtained absorbance levels were used as a string of values to correlate the reactivity to different microorganisms. IgM was found to be the most cross reactive antibody class, Pearson's r = 0.7-0.92, for very distant bacterial species such as Lactobacillus and E. coli.High correlation in IgG levels was found for Gammaproteobacteria and LPS (from E. coli) (r = 0.77 for LPS vs. P. aeruginosa to r = 0.98 for LPS vs. E.coli), whereas this correlation was lower in the control group (r = 0.49 for LPS vs. P. aeruginosa to r = 0.66 for LPS vs. E.coli). The correlation was also analyzed between total IgG and IgG subclasses specific for the same microorganism, and IgG2 was identified as the main subclass recognising different microorganisms, as well as recognising LPS. Upon correlation of IgG with IgA for the same microorganism absence of or negative correlation was found between bacteria-specific IgA and IgG in case of Lactobacillus and Staphylococcusgeni, whereas correlation was absent or positive for Candida albicans, Enterococcusfaecalis,Streptococcus species tested in professional athletes. Opposite results were obtained for the control group. Outlined here is a simple experimental procedure and data analysis which yields functional significance and which can be used for determining the similarities between microorganisms from the aspect of the humoral immune system, for determining the main IgG subclass involved in an immune response as well as for the analysis of different target populations.

• MeSH
• Adult MeSH
• Enzyme-Linked Immunosorbent Assay MeSH
• Immunity, Humoral MeSH
• Immunoglobulin A blood   MeSH
• Immunoglobulin G blood   MeSH
• Immunoglobulin M blood   MeSH
• Humans MeSH
• Adolescent MeSH
• Antibodies, Bacterial blood   MeSH
• Antibody Specificity * MeSH
• Athletes * MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Adolescent MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

PURPOSE: Primary selective IgM deficiency (sIgMD) is a primary immunodeficiency with unclear pathogenesis and a low number of published cases. METHODS: We reviewed clinical and laboratory manifestations of 17 sIgMD patients. Serum IgM, IgG, and its subclasses, IgA, IgE, antibodies against tetanus toxoid, pneumococcal polysaccharides and Haemophilus influenzae type b, isohemagglutinins, and T and B lymphocyte subsets, expressions of IgM on B cells and B lymphocyte production of IgM were compared with previously reported case reports and a small series of patients, which included 81 subjects in total. RESULTS: We found that some patients in our cohort (OC) and published cases (PC) had increased IgE levels (OC 7/15; PC 21/37), decreased IgG4 levels (OC 5/14), very low titers of isohemagglutinins (OC 8/8; PC 18/21), increased transitional B cell counts (OC 8/9), decreased marginal zone B cell counts (OC 8/9), and increased 21low B cell counts (OC 7/9). Compared with the PC (20/20), only two of five OC patients showed very low or undetectable production of IgM after stimulation. A majority of the patients had normal antibody production to protein and polysaccharide antigens, basic lymphocyte subset counts, and expression of surface IgM molecules on B cells. CONCLUSIONS: Low IgM levels are associated with various immunopathological disorders; however, pathogenic mechanisms leading to decreased IgM serum level in selective IgM deficiency remain unclear. Moreover, it is difficult to elucidate how strong these associations are and if these immunopathological conditions are primary or secondary.

• MeSH
• Autoimmunity MeSH
• B-Lymphocytes immunology   MeSH
• Adult MeSH
• Immunoglobulin E blood   MeSH
• Immunoglobulin G blood   MeSH
• Immunoglobulin M deficiency   metabolism   MeSH
• Infections immunology   MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Aged MeSH
• Immunologic Deficiency Syndromes immunology   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Screening for celiac disease (CD) dramatically improved when techniques able to measure blood autoantibodies against tissue transglutaminase 2 (TTG) were developed. Although typically increased in CD, these antibodies are not pathognomonic since they are also detected in several other autoimmune processes. IgA deficiency among celiac patients is more frequent than in general population (up to 25% vs 1-3%). This led to develop kits able to measure IgG-TTG, which until today represent a helpful diagnostic tool during diagnosis of CD in IgA deficient individuals. Today, commercial kits measuring IgG- TTG (and other) antibodies are widely available, are frequently used and create confusion in diagnosing CD in IgA-sufficient individuals. This is attributed to the fact that sensitivity and specificity of IgG-TTG is lower when applied to IgA-sufficient persons, and also because IgG-TTG is detected in several autoimmune disorders, with variable frequency and isotypes depending on the condition. Evidence analyzed indicate that to date available data: i) is insufficient to understand the difference of classes and subclasses detected in CD and other autoimmune conditions; ii) does not support the use of IgG-TTG for diagnosing CD in IgA-sufficient individuals and therefore iii) IgG should not be used in the routine diagnostic process of CD.

• MeSH
• Autoantibodies blood   MeSH
• Celiac Disease * diagnosis   physiopathology   prevention & control   MeSH
• IgA Deficiency * complications   MeSH
• Immunoglobulin A blood   MeSH
• Immunoglobulin G blood   MeSH
• Humans MeSH
• Predictive Value of Tests MeSH
• Serologic Tests MeSH
• Transglutaminases immunology   blood   MeSH
• Check Tag
• Humans MeSH

In view of the fact that insufficiency in immune response often correlates with poor prognosis, research in recent years has focused on the task of describing the precise status and function of the immune system and its possible effect on cancer patients. Although more than two thirds of treated patients respond to endocrine therapy, most patients with metastatic breast cancer develop a resistance to it. Estrogen modulates angiogenesis, partially through its effects on vascular endothelial growth factor (VEGF). It also appears that transforming growth factor-beta (TGF beta) could be another factor contributing to this resistance. TGF beta is a highly immunosuppressive factor that inhibits natural and specific immunity against tumors and stimulates the production of VEGF. The purpose of the study was to monitor immune responses in patients with hormone receptor-positive breast cancer who were resistant to hormone therapy. The examination of cellular components (CD4, CD8, HLA-DR, NK cells) and humoral immunity (IgG, IgG subclasses, IgA, IgM,). TGF beta and VEGF production were monitored with special attention, along with an analysis of the changes that occurred during the hormonal treatment. 68 patients included in the research project were implemented with routine cancer treatment with endocrine therapy. Basic parameters (the histological type and grade, the degree of expression of estrogen receptors (ER) and progesterone receptors (PR), human epidermal growth factor receptor 2 (HER2), and the proliferative marker) were established. Patients were evaluated by a cancer clinical immunologist to exclude immune disorders, allergic or autoimmune origin. TGF beta and VEGF were measured by ELISA and antitumor cellular immunity (CD4, CD8) was measured by flow cytometry. Patients who failed in the first line of hormone therapy treatment were considered as resistant to hormone therapy.Depression in cellular immunity was found especially in patients with resistance to endocrine therapy. In addition, immunoglobulin plasma levels were decreased (mainly IgG4 subtype). Most patients showed clinical symptoms of immunodeficiency (frequent infections of respiratory or urinary tract, herpetic infections). Significant increases in TGF beta and VEGF plasma were also detected.The correlation of these factors with resistance to hormonal therapy and the state of anticancer immunity could be helpful in the task of predicting resistance to hormonal therapy and could contribute to the selection of targeted immune therapy in cancer patients in the future.

• MeSH
• Immunity, Cellular MeSH
• Drug Resistance, Neoplasm * MeSH
• Adult MeSH
• Immunity, Humoral MeSH
• Middle Aged MeSH
• Humans MeSH
• Breast Neoplasms drug therapy   immunology   blood   MeSH
• Tamoxifen therapeutic use   MeSH
• Transforming Growth Factor beta blood   MeSH
• Vascular Endothelial Growth Factor A blood   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Female MeSH

Prevažne protilátkové primárne poruchy imunity predstavujú klinicky najčastejšie vrodené poruchy imunity (asi 70 % zo všetkých PID). Práve v tejto skupine sa vyskytujú aj štyri najčastejšie primárne poruchy imunity v detskom veku: selektívna deficiencia IgA, selektívna deficiencia podtriedy IgG, tranzientná hypogamaglobulinémia detského veku a porucha tvorby špecifických protilátok (proti polysacharidovým antigénom). Väčšina z týchto najčastejších PID však ostáva počas celého života dieťaťa asymptomatická. Klinicky najvýznamnejšou poruchou z tejto skupiny je spoločná variabilná imunodeficiencia (CVID), pre ktorú je charakteristická znížená koncentrácia sérových imunoglobulínov a variabilný vek klinickej manifestácie. Jedinou účinnou liečbou tejto skupiny PID je pravidelná substitučná liečba intravenóznymi, prípadne subkutánnymi imunoglobulínmi. Nevyhnutná je razantná a skorá antibiotická liečba infekčných komplikácií a v indikovaných prípadoch je možné aj profylaktické podávanie antibiotík.

Predominantly humoral primary immunodeficiencies are clinically the most frequent inherited immunodeficiencies (approximately 70 % of all PID). The four most frequent PID are also from this group: selective deficiency of IgA, selective deficiency of IgG subclass, transient hypogammaglobulinemia of infancy and the deficiency of specific antibodies (against polysaccharide antigens). Most patients with these frequent immune diseases are asymptomatic during the whole life. Clinically the most important disease from humoral PID is common variable immunodeficiency which is characterized by decreased serum level of immunoglobulins (especially IgG and IgA) together with variable onset of clinical symptoms. The unique efficient therapy of these PIDs is regular intravenous or subcutaneous substitution of immunoglobulins. The infectious complication should be treated soon and adequately with appropriate antibiotics, and in indicated cases, also prophylactic antibiotic treatment is recommended.