Salivary Immunoglobulins in Individuals with Common Variable Immunodeficiency

Abstract Oral manifestations of common variable immunodeficiency (CVID) are rare, have rarely been studied and have given controversial results. There are few data about IgA, IgG, and IgM antibody salivary levels in the literature, and there are few papers about the clinical impact of antibody deficiencies and CVID on the oral health of such patients. The aim of this study was to measure serum and salivary IgA, IgG, and IgM levels in CVID participants and controls, and to associate immunoglobulin levels with caries and periodontal disease. This was a case-control study involving 51 CVID individuals and 50 healthy controls. All participants underwent examination for dental caries and periodontal disease. Blood and whole saliva samples were collected on the same day of the oral examination. Serum IgA, IgM, and IgG levels were measured by turbidimetry and salivary IgA, IgM, and IgG titers were assessed by enzyme-linked immunosorbent assay. Incidences of caries and gingivitis were significantly higher in the CVID group than in the control group (p<0.05). Salivary and blood IgA and IgM titers were significantly reduced in the CVID group, but there was no association of salivary immunoglobulin levels with periodontal disease or with caries incidence (p>0.05 for both). Although CVID was associated with increased susceptibility to caries and gingivitis, it was not associated with low salivary levels of IgA and IgM.

Resumo As manifestações orais em pacientes com imunodeficiência comum variável (ICV) têm sido pouco estudadas e com resultados variados. Há escassos dados na literatura sobre os níveis de IgA, IgG e IgM na saliva, e pouco se sabe sobre o impacto clínico da deficiência destes anticorpos sobre a saúde bucal de pacientes com ICV. O objetivo deste estudo foi medir os níveis séricos e salivares de IgA, IgG e IgM em indivíduos com ICV e controles, e associar os níveis de imunoglobulinas com cárie e doença periodontal. Este foi um estudo de caso-controle, envolvendo 51 indivíduos ICV e 50 controles saudáveis. Todos os participantes foram examinados para cárie e doença periodontal. As amostras de sangue e saliva foram coletadas no mesmo dia do exame intraoral. Os níveis de IgA, IgM e IgG foram medidos por turbidimetria, e os títulos salivares de IgA, IgM e IgG foram avaliados através método imunoenzimático (ELISA). As incidências de cáries e gengivite foram significativamente maiores no grupo ICV do que no grupo controle (p<0,05). Os níveis de IgA e IgM salivares e no sangue foram significativamente reduzidos no grupo ICV, porém não houve associação dos níveis de imunoglobulina salivar com doença periodontal ou com a incidência de cárie (p>0,05 para ambos). Embora ICV foi associado com um aumento da susceptibilidade à cárie e gengivite, não estava associado com baixos níveis salivares de IgA e IgM.

Functional disruption of human leukocyte antigen II in human embryonic stem cell

BACKGROUND: Theoretically human embryonic stem cells (hESCs) have the capacity to self-renew and differentiate into all human cell types. Therefore, the greatest promise of hESCs-based therapy is to replace the damaged tissues of patients suffering from traumatic or degenerative diseases by the exact same type of cells derived from hESCs. Allo-graft immune rejection is one of the obstacles for hESCs-based clinical applications. Human leukocyte antigen (HLA) II leads to CD4+ T cells-mediated allograft rejection. Hence, we focus on optimizing hESCs for clinic application through gene modification. RESULTS: Transcription activator-like effector nucleases (TALENs) were used to target MHC class II transactivator (CIITA) in hESCs efficiently. CIITA(-/-)hESCs did not show any difference in the differentiation potential and self-renewal capacity. Dendritic cells (DCs) derived from CIITA(-/-)hESCs expressed CD83 and CD86 but without the constitutive HLA II. Fibroblasts derived from CIITA(-/-)hESCs were powerless in IFN-γ inducible expression of HLA II. CONCLUSION: We generated HLA II defected hESCs via deleting CIITA, a master regulator of constitutive and IFN-γ inducible expression of HLA II genes. CIITA(-/-)hESCs can differentiate into tissue cells with non-HLA II expression. It's promising that CIITA(-/-)hESCs-derived cells could be used in cell therapy (e.g., T cells and DCs) and escape the attack of receptors' CD4+ T cells, which are the main effector cells of cellular immunity in allograft.

Successful Renal Transplantation with Desensitization in Highly Sensitized Patients: A Single Center Experience

Intravenous immunoglobulin (IVIG) and/or plasmapheresis (PP) are effective in preventing antibody-mediated rejection (AMR) of kidney allografts, but AMR is still a problem. This study reports our experience in living donor renal transplantation in highly sensitized patients. Ten patients with positive crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Eight patients were desensitized with pretransplant PP and low dose IVIG, and two were additionally treated with rituximab. Allograft function, number of acute rejection (AR) episodes, protocol biopsy findings, and the presence of donor-specific antibody (DSA) were evaluated. With PP/IVIG, six out of eight patients showed good graft function without AR episodes. Protocol biopsies revealed no evidence of tissue injury or C4d deposits. Of two patients with AR, one was successfully treated with PP/IVIG, but the other lost graft function due to de novo production of DSA. Thereafter, rituximab was added to PP/IVIG in two cases. Rituximab gradually decreased PRA levels and the percentage of peripheral CD20+ cells. DSA was undetectable and protocol biopsy showed no C4d deposits. The graft function was stable and there were no AR episodes. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful living donor renal transplantation in sensitized recipients.

Epstein-Barr Virus Antibodies in Kawasaki Disease

The prevalent ages at onset for Kawasaki Disease (KD) and Epstein-Barr virus (EBV) infection are known to be similar in Korea and Japan. We evaluated the correlation between EBV infection and KD. The antibodies to EBV such as anti-viral capsid antigen (VCA) IgG and IgM, anti-diffuse and restricted early antigen IgG (anti-EADR IgG), and the anti-EBV determined nuclear antigen IgG (anti-EBNA IgG) were examined in 29KD patients at five separate times sequentially during a period of one year, and also in 14 other children with a past history of KD. The results of each group were compared with those of age-matched controls. The positive rates of anti-VCA IgG and IgM at presentation in the KD patients were 41.4% (12/29) and 0% (0/29), respectively. Only one patient was found to be anti-VCA IgM-positive within two months. There were no cases of anti-VCA IgG except one, anti-EADR IgG and anti-EBNA IgG positive to negative seroconversion during the year. The children with a past history of KD showed higher anti-EBNA IgG-positive rates than the controls (p=0.04). There was no difference in the seropositive rates of the antibodies to EBV, cytomegalovirus, herpes simplex virus and herpes zoster virus. In conclusion, children with KD were noted to have normal immune responses to EBV infection. Children with a past history of KD seemed to be infected with EBV at a later age than children with no history of KD.

An immunohistochemical study of chromogranin A and Sp-1 immunoreactive cells in the gastrointestinal tract of ovariectomized rats

The changes on the regional distributions and frequencies of two types of chromogranin, chromogranin A (CGA) and bovine Sp-1 chromogranin (BCG)-immunoreactive (IR)cells in gastrointestinal (GI)tract of osteoporotic Sprague-Dawley rat induced by ovariectomy were studied by immunohistochemical methods. The experimental animals were divided into two groups, one is non-ovariectomized group (Sham)and the other is ovariectomized group (OVX). Samples were collected from each part of GI tract at 10th week after ovariectomy or sham operation. CGA-IR cells were restricted to the stomach regions with various frequencies regardless of ovariectomy except for the fundus of OVX in which no cells were detected. In addition, BCG-IR cells were also restricted to the pylorus and duodenum regardless of ovariectomy. A significantly decrease of CGA IR cells was detected in OVX compared to that of Sham in both fundus and pylorus, and BCG-IR cells were also significantly decreased in the duodenum(p<0. 05). However, in the pylorus, BCG-IR cells in OVX showed similar frequency compared to that of Sham. In conclusion, the abnormality in density of chromogranin, a generally used GI endocrine cell marker, detected in this study may contribute to the development of GI symptoms in osteoporosis such as impairments of calcium and some lipids, frequently encountered in patients with postmenopausal osteoporosis.

Influência do tipo de parto sobre a concentração de imunoglobulinas A, G e M no colostro materno / Influence of type of delivery on A, G and M immunoglobulin concentration in maternal colostrum

OBJETIVO: Verificar a influência do tipo de parto sobre a concentração das imunoglobulinas (Ig) A, G e M no colostro materno. MÉTODOS: Foram selecionadas 82 puérperas com idade cronológica entre 21 e 41 anos, idade gestacional de 37 ou mais semanas, paridade até IV gesta, bom estado nutricional e sem patologias associadas durante a gestação e o puerpério. Foram também critérios de inclusão para os recém-nascidos: peso > 2.500 g, escore de Apgar > 7 no primeiro minuto e aleitamento materno exclusivo durante o período da internação. As puérperas foram divididas em três grupos: A - parto vaginal; B - cesárea precedida de trabalho de parto; e C - cesárea eletiva. O colostro foi colhido manualmente entre 48 e 72 horas pós-parto. IgA, IgG e IgM foram dosadas pela técnica de ELISA RESULTADOS: Não se observou diferença significativa entre os tempos de coleta do colostro nos três grupos maternos estudados. Quanto menor o tempo de coleta, maior foi a concentração de IgA no colostro materno; quanto menor a paridade, maior foi a concentração de IgA e IgM no colostro materno. O grupo de puérperas submetidas a cesárea precedida de trabalho de parto apresentou concentração mais elevada de IgA no colostro do que o grupo de puérperas que havia dado à luz por parto normal. A concentração de IgM e IgG no colostro materno não foi influenciada pelo tipo de parto. CONCLUSAO: A ocorrência do trabalho de parto, somada ao estresse cirúrgico, induz a uma concentração mais elevada de IgA no colostro materno na puérpera submetida a cesárea precedida de trabalho de parto.

X-linked Severe Combined Immunodeficiency Syndrome: The First Korean Case with gamma c Chain Gene Mutation and Subsequent Genetic Counseling

X-linked severe combined immunodeficiency (X-SCID) is a rare, life-threatening immune disorder, caused by mutations in the gamma c chain gene, which encodes an essential component of the cytokine receptors for interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21. A 13-month-old boy with recurrent infections who had reduced serum immunoglobulin levels and decreased numbers of CD3, CD16/56 cells was evaluated for gamma c chain gene mutation and protein expression. The patient had a C-to-T point mutation at nucleotide position 690, one of the hot spots, resulting in a single amino acid substitution of cysteine for arginine (R226C), as determined by direct sequencing and PCR-RFLP. The patient's mother was a heterozygous carrier. Percutaneous umbilical cord blood sampling was performed at the 6-month of gestation in a subsequent pregnancy. As the immunophenotype of the fetus showed an identical pattern, the pregnancy was terminated and genetic analysis of the abortus confirmed recurrence. This is the first report of the molecular diagnosis of X-SCID in Korea. Genetic analysis of the gamma c chain gene is useful for definite diagnosis and genetic counseling for X-SCID.

Hemophagocytic Syndrome Associated with Kikuchi's Disease

A 13-yr-old female was admitted to our hospital with fever, seizure, and cervical lym-phadenopathy. Laboratory data showed pancytopenia, elevation of serum transaminase, lactate dehydrogenase, triglyceride, and ferritin levels. Lymph node biopsy revealed features of Kikuchi's disease and there were signs of histiocytosis and hemophagocytic phenomenon in bone marrow. She recovered after treatment with intravenous immunoglobulin and corticosteroids therapy. Hemophagocytic syndrome can be associated with Kikuchi's disease especially in childhood and seems to have a less aggressive clinical course and better prognosis.

Degradation of immunoglobulins, protease inhibitors, and interleukin-1 by a secretory proteinase of Acanthamoeba castellanii

The effect of a secretory proteinase from the pathogenic amoebae Acanthamoeba castellanii on hosts defense-oriented or regulatory proteins such as immunoglobulins, interleukin-1, and protease inhibitors was investigated. The enzyme was found to degrade secretory immunoglobulin A (sIgA), IgG, and IgM. It also degraded interleukin-1alpha (IL-1alpha) and IL-1beta. Its activity was not inhibited by endogenous protease inhibitors, such as alpha2-macroglobulin, alpha1-trypsin inhibitor, and alpha2-antiplasmin. Furthermore, the enzyme rapidly degraded those endogenous protease inhibitors as well. The degradation of hosts defense-oriented or regulatory proteins by the Acanthamoeba proteinase suggested that the enzyme might be an important virulence factor in the pathogenesis of Acanthamoeba infection.

Diagnostic significance of immunoglobulins and adenosine deaminase in pleural effusion.

OBJECTIVES: 1) To evaluate the diagnostic significance of ELISA for detection of antibodies to antigen A60 of Mycobacterium tuberculosis and adenosine deaminase (ADA) in patients with pleural effusion without prior history of tuberculosis, 2) To study the importance of the above tests in patients with HIV infection and pleural effusion. METHOD: Eighty one patients with pleural effusion were studied. In addition to diagnostic paracentesis and pleural biopsy, pleural fluid specific IgG, IgM, IgA against antigen A60 and fluid ADA were estimated. HIV testing (ELISA) was done in all patients. RESULTS: Out of 81 patients, 13 were HIV positive. IgG anti A60 had a sensitivity and specificity of 90.71% and 33.33% respectively. The combination of IgG and IgM had a sensitivity and specificity of 96.3% and 55.55% respectively. IgA alone or in combination did not offer any diagnostic advantage. ADA had a sensitivity and specificity of 76% and 60% respectively. In presence of HIV infection, antibodies against A60 had a sensitivity of 76.92% and ADA had a sensitivity of 61.54%. CONCLUSIONS: In patients with pleural effusion, immunoglobulins against antigen A60 have a limited diagnostic role with high false positive rates. Co infection with HIV further reduces the value of above diagnostic tests.

Perfil metabólico en afectados por cenizas volcánicas / Metabolic perfile of the areas affected by the ashes of Hudson volcano

En 1991 entró en erupción el volcan Hudson, situado en la república de Chile. La columna eruptiva expulsó cenizas colcánicas que arrastradas por los fuertes vientos con dirección noroeste sudeste afectó toda la Patagonia tanto Chilena como Argentina, llegando a las Islas Malvinas (FALKLANDS) y Sur de la provincia de Buenos Aires.Estas cenizas afectaron la salud de la población, por lo cual se avaluó el deterioro producido en células y tejidos por la probable destrucción de organelas tales como lisosomas y vacuolas con la consiguiente eliminación de enzimas como la Fosfatasa ácida y la beta glucuronidasa. Se cuantificaron las inmunoglobulinas sanguíneas G,A,M yE y las fracciones del complemento C3 C4. Se estudiaron 48 pacientes en los cuales las concecuencias producidas por inhalaciòn son más físicas que bioquímicas. No se observaron modificaciones de las encimas. Con respecto a la fracción del complemento C3 se apreció una tendencia a valores bajos, mientras el comportamiento de la fracción C4 es normal. Los valores de las inmunoglobulinas G estan dentro de los límites normales, pero con tendencias a valores bajos. No así la inmunoglobulina A que muestra valores normals. Los valores de la inmunoglobulina E estan aumentados por sobre los valores normales

Changes in membrane fluidity induced by binding of immunoglobulins to sperm Fc receptors.

Receptors for Fc region of immunoglobulins (FcR) are reported to be present on spermatozoa, and also detected in seminal plasma, however their function is still not known. Since various changes in sperm membrane architecture during maturation and passage through female genital tract are reported, experiments were conducted to study the membrane fluidity changes in sperm subsequent to ligation of surface FcR with immunoglobulin and its derivatives. This paper reports that interaction with IgG restricts rotational mobility of cell surface proteins and membrane lipids as studied by EPR spectroscopy using spin probes. Decrease in fluidity was much more pronounced in the presence of aggregated IgG due to crosslinking of sperm FcR by aggregated IgG.

Potent stimulation of murine B cells to proliferate and to secrete immunoglobulins by a lipoteichoic acid-like molecule produced by Clostridium botulinum C and D

Bacterial products have served as important immunological tools to study ly,phocyte activation. The lipopolysaccharides of the Gram-negative bacteria are well known to be potent activators of B lymphocytes. Several Gram-positive bacteria produce exotoxins that are superantigens for T cells. In the present study, we demonstrate that the Gram-positive bacteria Clostridium botulinum C and D produce a high molecular weight mitogen (Cb mitogen) that is a potent activator of murine B lymphocytes. The Cb mitogen was discovered as a consequence of our attempt to investigate a possible superantigen activity present in the botulinum exotoxins. We observed initially that mouse spleen cells were strongly stimulated to proliferate by culture supernatants of C. botulinum C and D. However, the characterization of the responding cell ruled out superantigen because only the B lymphocytes were stimulated to proliferate and to secrete immunoglobulins, and they did so independent of T cell help. In addition, the molecular characterization of the Cb mitogen demonstrated that the purified botulinum toxin was devoid of mitogenic activity. In contrast, the fractionation of the culture supernatant of C. botulinum C in an FPLC Superose 12 column indicated that the Cb mitogen was present in the void volume of the column (MW ò 300 kDa) which had no toxigenic activity. However, the fractions containing molecules of 150 KDa were highly toxic for mice and had no mitogenic activity...

Mecanismos de defesa da bile / Defense mechanisms of the bile

Nesta revisao sao explicados cada um dos quatro mecanismos de defesa da bile contra a infecçao por microorganismos patógenos, bem como suas açoes integradas. Nesse contexto, incluem-se as barreiras anatômicas (complexos unitivos e esfíncter de Oddid), os mecanismos físicos (fluxo biliar e muco), os fatores químicos (sais biliares) e os mecanismos imunológicos (células de Kupffer e imunoglobulina A secretada). A quebra do funcionamento harmônico desses mecanismos pode levar a sérias infecçoes. Nesse sentido, o aumento da pressao intra-biliar (causada por obstruçao parcial ou completa do fluxo biliar) e doenças do parênquima hepático desempenham papel fundamental. Dessa forma, confirma-se a importância da preservaçao desses mecanismos de defesa no indivíduo saudável.

Estudio inmunogenético de una familia con escleroma / Inmunogenetic study in family with scleroma

Se presenta una familia con 6 miembros afectados de escleroma. El estudio inmunogenético revela la existencia de un antígeno del complejo principal de histocompatibilidad (HLA) en todos ellos (DQ3), lo que implica inmunidad celular alterada. los niveles de inmunoglobulinas muestran un aumento de la IgG que puede corresponder a alguna alteración de la inmunidad humoral agregada relacionada, ya sea con factores extrínsecos o con factores intrínsecos no determinados por el complejo principal de histocompatibilidad (HLA).

Generación de hibridomas humano-humano secretores de anticuerpos empleando la línea celular linfoblastoide W1-L2-729 HF2 / Genaration of antibody secretor human-human hybridomas using W1-L2-729 HF2 lymphoblastic cell line

En el presente trabajo se informa por primera vez en Cuba, la producción de hibridomas humano-humano secretores de inmunoglobulinas a partir de la fusión de linfocitos de ganglios linfáticos axilares de paciente con cámcer de mama con células de línea celular linfoblastoide B humana W1-L2-729HF2. En 3 de las 4 fusiones realizadas se obtuvieron hibridomas con crecimiento celular en 196 de los 569 pozos sembrados con el producto de las fusiones. Los primeros híbridos se observaron al final de la primera semana, aunque la mayoría se detectó en la segunda y tercera semanas de haberse realizado la fusión. De los 196 pozos con crecimiento celular, 120 eran secretores de inmunoglobulinas. El nivel de secreción de los híbridos clonados fue desde 4,5 hasta 8,0 *g/mL por 10 6 células. La naturaleza híbrida se determinó por análisis cromosómico y por la clase de inmunoglobulina producida. No se detectaron anticuerpos específicos contra los antígenos intracelulares o localizado en la superficie celular de las diferentes líneas celulares tumorales humanas empleadas en el estudio

Certain immuno-haematological effects of laser irradiation.

The effects of low power He-Ne laser of 7 milliwatt power on certain immuno-haematological parameters were studied using fresh human blood samples. The parameters studied include electrophoretic mobility of haemoglobin, quantification of immunoglobulins, soluble immune complex levels, blood grouping, Rh typing and neutrophil function tests. Our results show that there is no significant change in the parameters studied after laser irradiation for 60 minutes except changes in the electrophoretic mobility of haemoglobin. In addition laser exposure causes haemolysis in all the samples examined.

Distribution of lymphocytic subpopulations infiltrated in thyroid glands of Graves' disease

We studied ninety cases of thyroid glands both histopathologically and by immunohistochemical methods in patients with Graves' disease using B and T cell markers to evaluate the role of lymphocytic subpopulation. Females were affected more frequently than males with a ratio of 6.5:1, and usually the females were younger than the males at the time of surgery. The heavier the lymphocytic infiltration, the higher was the percentage of germinal center formation or fibrosis. The degree of lymphocytic infiltration was also related to the titers of antithyroglobulin or antimicrosomal antibodies. T cells were mostly scattered individually or in small groups between the follicles; however, in the severely infiltrated group, the major pattern was in clusters. T8 positive cells were more abundant than T4 positive cells, and their distribution pattern was accordant with T11 positive cells. Immunoglobulin synthesizing B cells were positively stained in 47 of 94 cases tested and IgG was the most predominant. In the mild and moderate lymphocytic infiltration groups, IgM was mostly stained at the mantle zone or in the lymphoid cluster of the interfollicular stroma, whereas IgM positive cells were present exclusively in the germinal center of the severely infiltrated group. The results of our study indicate that the major lymphocyte subpopulation in Graves' disease is B lymphocytes, and the degree of T lymphocytic infiltration correlated better with titers of antimicrosomal antibody than antithyroglobulin.