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PubMed1996

[Immunologic characteristics of undernutrition. I. The undernourished patient in nutritional recovery].

Malnutrition in children is a well known critical factor that determines immunocompetence changes with altered immune response and higher risk to many diseases, especially in developing countries. Moreover, it is related to increased morbi-mortality rates mainly due to infections. For those reasons, 12 undernourished children, age 5 to 24 months were studied along 8 weeks at the Nutritional Recovery Center of Chiquinquira Hospital in Maracaibo, Venezuela. There were 5 cases of kwashiorkor, 5 marasmatics, 1 mixed marasmus/kwashiorkor and 1 case with moderate malnutrition. After a control blood sample was taken and cutaneous tests were done, a nutritional recovery program was began. At regular time intervals and at the end of the study, tests were done again by measuring seric immunoglobulins (IgG, IgA, IgM), secretory IgA (IgAs), C3 and C4 complement, lymphocytic sub-populations, and auto antibodies; cutaneous hipersensitivity tests were also done. As a control group, 10 apparently healthy children of matching age and sex were also studied with the same parameters. Results show that basal seric Igs did not differ significantly from the control group and did not change along the recovery program period, but there was a significant decrease in IgAs at all times of the study. C4 did not change and C3 was lower than control (p < 0.05) but returned to normal value at the end of the recovery period. CD3 and CD4 lymphocytes showed the same pattern. Only two patients showed positive skin tests and auto antibodies were not detected. It is concluded that there is indeed an altered immune competence with low levels of C3, IgAs, and CD3-CD4 lymphocytes that is reversible after nutritional recovery.

Antigens, CD↗

PubMed2003

Serum alpha1-antitrypsin but not complement C3 and C4 predicts chronic inflammation in hemodialysis patients.

BACKGROUND: We studied whether predialysis serum levels of positive acute phase markers such as alpha1-antitrypsin (AT), and complement components C3 and C4 could identify the presence of chronic inflammation in maintenance hemodialysis (HD) patients. METHODS/RESULTS: In 103 stable HD patients, AT directly correlated with C-reactive protein (CRP) (P < 0.005), alpha1 acid-glycoprotein (P < 0.005), fibrinogen ( P < 0.05), lipoprotein (a) (P < 0.01) and von Willebrand factor antigen (P < 0.05), while C3 and C4 were not related to any of these inflammatory markers. In the patients with elevated CRP and hypoalbuminemia, the mean AT value of 1.74 +/- 0.50 g/L was higher (P = 0.008) than that of 1.38 +/- 0.27g/L in the subjects with normal CRP and albumin. Using the above cut-off levels, the positive and negative predictive values of AT on the presence of severe inflammation were 0.86 and 0.62, respectively, and the sensitivity and specificity were 86% and 73%, respectively. CONCLUSION: Serum AT levels above 1.74 g/L and below 1.38 g/L may select the HD patients with severe inflammation from those without. Measurements of C3 and C4 are not helpful in this situation.

Adolescent↗

PubMed1998

Genetic and immunologic studies of patients on procainamide.

Forty (40) patients with cardiac arrhythmias receiving procainamide (PA) therapy and 24 patients who were receiving other drugs for their cardiac disorders were investigated for class II HLA phenotypes and their DRB1*04 and DQB1*03 subtypes. Other genetic marker evaluations in the PA patients included: 1) class III MHC C4A and C4B null alleles of complement; and, 2) acetylation phenotype. Twenty (20) of the PA patients were also tested for the ability of their stimulated cells to secrete Interleukin-1 (IL-1 beta) and tumor necrosis factor (TNF alpha). We also examined the spontaneous production of these cytokines by peripheral blood leukocytes (PBL) from patients who were receiving chronic PA treatment. The results revealed no association of acetylation phenotypes with the class II HLA phenotypes nor class III MHC C4 allotypes in these patients. The results did show a significant increase in class III C4 complement allotypes in the PA patients when compared to the controls. The results also showed a significant increase in autoantibodies and DQw3 phenotypes in the PA patient group when compared to control populations. Results of spontaneous IL-1 and TNF production suggested there may be an association of select class II HLA phenotypes in some patients and this may be relevant to host responsiveness to PA treatment.

Acetylation↗

PubMed2005

Proinflammatory factors in saliva as possible markers for periodontal disease.

Studies have indicated that host inflammatory proteins, enzymes and indicators of bone metabolism present in saliva differ in different types of periodontal disease. However, the number of markers analyzed was limited and the effect of edentulousness was not examined. We measured the concentration of host inflammatory proteins: C-reactive protein (CRP), C3 and C4 complement components, alpha-2-macroglobulin (alpha-2M) and tumor-necrosis factor (TNF) in unstimulated saliva of 14 periodontally healthy (PH), 9 edentulous persons (EP), 10 patients with chronic periodontitis (CP) and 18 with aggressive periodontitis (AgP). TNF was below the level of detection in all samples except one. Edentulous persons and patients with CP had significantly reduced concentrations of CRP, C3 and alpha-2M. Edentulous persons and AgP patients had lower C4 concentrations. We can conclude that edentulous persons and CP patients have reduced salivary concentrations of host inflammatory proteins. These findings suggest that a reduction in host responsiveness might play a role in the pathogenesis of CP.

Adult↗

PubMed1981

Enzymatic treatment transforms trypomastigotes of Trypanosoma cruzi into activators of alternative complement pathway and potentiates their uptake by macrophages.

In the absence of bound antibody, trypomastigote bloodstream forms of Trypanosoma cruzi fail to activate the alternative complement pathway. We now demonstrate that treatment with trypsin and, to a lesser extent, with sialidase converts these protozoa into activators of the pathway, as judged by their lysis in normal sera or sera genetically deficient in fourth or second component of complement (C4 or C2) and their Mg2+-dependent consumption of C3 as measured by crossed immunoelectrophoresis. In addition, after pretreatment with enzyme and incubation in C5-deficient serum, trypomastigotes were shown to possess both C3 and properdin factor B (B) on their surface as judged by immunofluorescence. Requirement for the late components C5-C9 was suggested by the failure of C5-deficient sera to lyse trypsin-treated parasites. The inability to activate the alternative complement pathway was regained by these organisms after incubation in vitro. This restoration of insusceptibility was inhibited when puromycin was included in the culture medium. Treatment of the trypomastigotes with trypsin also potentiated their uptake by mouse peritoneal macrophages without apparent interference with their capacity to differentiate and multiply inside the cell. These findings suggest that untreated trypomastigotes normally escape recognition by the alternative pathway in vivo because of the presence on their surface of trypsin- and sialidase-sensitive regulatory molecules, the expression of which is dependent on protein synthesis.

Animals↗

PubMed1994

A new PCR-based typing of the Rodgers and Chido antigenic determinants of the fourth component of human complement.

The Rodgers (Rg) and Chido (Ch) blood groups are antigenic determinants of the fourth component of human complement C4. They are associated with the two isotypes of C4, C4A and C4B, respectively. They serve as markers to distinguish C4A from C4B as well as for the definition of subtypes of common and rare allotypes. As an alternative to the serological typing method using human alloantisera, a PCR typing procedure with sequence-specific primers (PCR-SSP) was designed. The method was tested on selected DNA samples from individuals with well-defined C4 allotypes. No false-positive or false-negative typing results were obtained and all the determinant combinations could be distinguished. The PCR genotyping allowed the detection of all Rg/Ch sequence determinants of each isotype. Thus, reverse antigenicity could also be established in the presence of other C4 allotypes without a segregation study. To exclude the possibility that PCR-typed determinants originate from a non-expressed C4 null gene, a sequence-specific PCR was established detecting a 2-bp insertion in exon 29 described previously as a cause for C4A non-expression. PCR Rg/Ch genotyping provides a fast and efficient method for routine typing in HLA haplotype and disease association studies.

Alleles↗

PubMed1990

Interleukin-1-mediated enhancement of mouse factor B gene expression via NF kappa B-like hepatoma nuclear factor.

Complement factor B, a serine protease playing a pivotal role in alternative pathway activation, is an acute-phase plasma protein. Previous studies have revealed that interleukin-1 (IL-1) mediates, at least in part, the acute-phase induction of factor B expression and that the IL-1-responsive element resides in the region between -553 and -478 relative to the transcription initiation site of the mouse factor B gene. In this paper, we demonstrate a specific binding site for a nuclear factor of human hepatoma HepG2 cells in this region of the factor B gene, using gel shift and methylation interference analysis. The nucleotide sequence of the binding site is closely similar to the NF kappa B or H2TF1 binding motif. The binding activity of HepG2 showed very similar specificity to that of NF kappa B or H2TF1, as shown by a competition binding assay, and was induced by IL-1 alpha treatment. A synthetic oligonucleotide corresponding to this binding site, as well as a similar sequence found in another class III complement C4 gene, conferred IL-1 responsiveness on the minimal factor B promoter. In contrast, a mutated oligonucleotide that could not bind to the HepG2 nuclear factor did not confer IL-1 responsiveness. These results suggest that IL-1 induces factor B expression via NF kappa B or a closely related factor in hepatocyte nuclei.

Animals↗

PubMed1972

In vitro synthesis of a regulator of mammalian gene expression.

Peritoneal cells isolated from guinea pigs homozygous for a deficiency of the fourth component of complement (C4), produce in vitro a factor that induces the synthesis and secretion of functionally active human C4 by a human cell. This factor appeared to switch on production of C4 in the responsive cell without affecting total protein synthesis. The regulator factor is not species specific, inasmuch as guinea pig regulator affected a corresponding human gene function. Both synthesis of the factor and the response to it were inhibited by actinomycin D. The amount of regulator recovered from genetically deficient cells was about 5-10 times that recovered from normal guinea pig cells.

Amino Acids↗

PubMed1992

HLADR5 and C4BQO high frequency and antinuclear antibodies positivity in patients with 21 hydroxylase deficiency from Campania region.

HLA haplotypes, complement C4 factor and factor B immunochemical concentrations and autoantibodies titer have been studied in six patients with mild congenital adrenal hyperplasia (MC-AH), in two patients with classical congenital adrenal hyperplasia (CCAH) and in their parents. A high frequency of DR5 and C4BQO alleles have been found in MCAH patients. Moreover, C4BQO allele is carried out in three out of four cases associated with DR5. In the two CCAH patients we found a B51 and a B14 allele, the last one usually described in the non classical form of the disease in population of different ethnic origin. Signs of autoimmunity in some patients and parents have been found. C4 null alleles were several-fold more frequent among our patients with respect to the same ethnic control group and the autoantibody positivity could be the result of an altered immune regulation. The presence of a positive correlation between cortisol basal levels and C4 and Bf concentrations in the six MC-AH patients suggests an interrelationship between hormonal factors and immunological findings in this disease. Our finding about HLA antigens not previously described in this syndrome may stimulate more profound studies by genomic and cDNA probes.

17-alpha-Hydroxyprogesterone↗

PubMedDate not supplied

[Humoral indices of the inflammatory process in psoriasis].

Immune complexes were determined in 104 patients with psoriasis, aged between 19 and 55 years. Duration of the disease, extension of lesions, and effects of infections preceding skin eruptions were considered. The studies showed the activation of immunological mechanism in psoriasis manifested by the increase in IgG and IgA levels, unchanged IgM levels, significantly more frequent negative values of IgD, significant increase in complement C4 component levels in all forms of the disease, and C3 activation in the acute and generalized chronic form. A significant increase in alpha 2 Mg was noted independently of the evolution and extension of skin lesions. An increase in alpha 1 AT was noted only in the initial phase of skin eruptions. An increase in Hp, Cr, CRP, and CIC was noted only during exacerbations. CIC were noted most frequently in postinfection psoriasis.

Adult↗

PubMed1997

Immunological monitoring of dry-cleaning shop workers--exposure to tetrachloroethylene.

A panel of immunological parameters has been examined in a group of dry-cleaning workers (n = 21) and in a control group of administrators (n = 16) from the same plant. The results were also compared to long-term laboratory reference values (LRV) (n = 14-311). External exposure to tetrachloroethylene (PER) was represented by TWA (8 h) values in the range 11-752 mg PER/m3. Biological monitoring showed an amount from 9 to 344 mg PER/m3 in exhaled air by the end of workshift. 1. The exposed dry-cleaning workers compared to the controls from the plant had statistically significant changes in metabolic activity of phagocytes, alpha 2-macroglobulin, C3 and C4 complement component, salivary secretory IgA, and blastic transformation test. Most of the values were within the range of normal values. 2. The exposed dry-cleaning workers had several abnormal immune parameters compared to the long-term laboratory values (LRV) especially in the alpha 2-macroglobulin, C3 and percentage of T-lymphocytes. Most of the changes, even those that were statistically significant, were still within the range of normal values, but they might be classified as trends or shifts away from normal (spontaneous blastic transformation, absolute number of phagocyting cells, coeruloplasmin, circulating immunocomplexes, serum lysozyme). 3. The non-exposed controls from the same plant showed both quantitative and qualitative differences when compared to the LRV. Changes were seen in IgG, C4, CSI and in increased spontaneous metabolic activity of leucocytes, total leucocyte count, absolute number of phagocyting cells, alpha 2-macroglobulin, prealbumin, C4, circulating immunocomplexes and serum lysozyme. 4. The distribution analysis of all results detected a large number of abnormal values in both groups, more in the at-risk group. 5. As inhalation was the main route of PER exposure it was concluded that the changes might represent aspects of the response of the respiratory immune system, mainly of the alveolar macrophages. Additional postinfection effects could not be excluded in both studied groups. Individual differences in immune reactivity as well as individual range of exposure should be taken into consideration.

Adult↗

PubMed1989

Trichorhinophalangeal syndrome type I and systemic lupus erythematosus with complement C4A homozygous null alleles in the same family.

A three generation family from northern Sweden with both trichorhinophalangeal syndrome type I (TRP I) and systemic lupus erythematosus (SLE)-like syndrome with complement C4 homozygous null alleles is described. Five family members in three generations were affected by the TRP I syndrome, indicating autosomal dominant inheritance. Two members had clinical and laboratory signs of SLE and two other members SLE-like syndrome. All living family members in the first and second generation had homozygous C4A null alleles. In three of the adults the two syndromes occurred simultaneously, probably in this family by coincidence.

Abnormalities, Multiple↗

PubMedDate not supplied

[A thymus extract (thymomodulin) in the prevention of childhood asthma].

41 children aged 2-12 years affected with bronchial asthma, have been treated orally with a thymus extract for three months (sep.-oct.-nov. 1980); a further period of treatment has been repeated during the month of March 1981. The following immunologic tests have been performed before therapy, 2 months after therapy withdrawal and 12 months after the second therapeutical discontinuance: plasmatic immunoglobulins (P. Ig), C3-C4 complement's factors, E-rosette forming cells (both active and total), surface immunoglobulins (IgS), PHA lymphocyte stimulation. Periodic anamnestic and clinical controls of patients revealed a significant reduction of asthmatic attacks during the months of observation, in comparison with the crises remarked in the same period of the previous year (the mean number of crises per child being 6 and 0.7 respectively before and after treatment, P less than 0.001). The immunologic tests, despite the clinical results, did not show significant modifications at the 1st control. Nevertheless the control carried out 12 months after the second therapeutical withdrawal demonstrated: IgG and IgM plasmatic levels significantly increased (1097 +/- 63 vs 906 +/- 45 and 122 +/- 10 vs 104 +/- 10 respectively, P less than 0.02) while IgE, C3-C4 plasmatic levels significantly decreased (232 +/- 57 vs 396 +/- 71, 132 +/- 6 vs 162 +/- 7, 22 +/- 2 vs 30 +/- 2 respectively, P less than 0.005). No side effects have been seen in all the patients treated.

Asthma↗

PubMed1986

The functional inhibition of activated C1 inhibitor in normal human serum causes spontaneous consumption of the complement components C2, C3, C4, and factor B.

The human complement components C1r, C1s, C4, C3, factor B, and/or activated C1INH were functionally blocked in normal human serum (NHS) and EGTA- or EDTA-treated NHS by polyclonal monospecific Fab'-fragments to the individual components. The results of inhibition experiments are compatible with the formation of a classical pathway fluid-phase C3 convertase (C4b2a) spontaneously generated by the inhibition of activated C1INH. This process in both NHS and EGTA-NHS was accompanied by the consumption of C2, C4, C3, and factor B but only by poor enhancement of C5 conversion. Blocking subcomponent C1r, completely inhibited spontaneous activation of the complement components, indicating that the control of C1r hydrolysis is the essential role of activated C1INH as a regulator of C1 activation in NHS. Non-complement serum proteases were inactive during the initiation of the activation process. The presence of blood cells during functional inhibition of activated C1INH in NHS slightly decreased the consumption of C3 but not of C2 and C4.

Angioedema↗

PubMed1986

Rheumatoid arthritis with pleural effusion includes a subgroup with autoimmune features and HLA-B8, Dw3 association.

Twenty-eight patients with rheumatoid pleural effusion were investigated to examine the frequency of HLA antigens as compared with 56 rheumatoid arthritis (RA) patients without this intrathoracic manifestation of RA and with 283 healthy controls. HLA-B8 was strongly associated with the presence of pleural effusion (PE) in RA patients. A high prevalence (71%) of B8/Dw3 was found among male RA patients of the PE group in whom the joint disease had begun at an age over 50 years and who also had besides pleuritis other intrathoracic manifestations of RA associated with high rheumatoid factor titres and low complement (C4) levels in sera. Actually, the HLA-B8 association was not seen in the rest of the PE group. The finding may be related to the heterogeneity of RA, a male subgroup of the disease being characterized by multiple intrathoracic manifestations and genetically associated with the large group of autoimmune disorders, such as SLE, characterized by high prevalences of HLA-B8 and D(R)3.

Adult↗

PubMed1990

[Components of human complement system. Testing and isolation of C3 and C5].

Modified reagents for testing the hemolytic activity of human complement components, C3 and C5, have been obtained. These reagents were obtained by treatment of human blood serum pools with a saturated solution of KBr (reagent R3) or 2 M KSCN and denaturated yeasts (reagent R5). These reagents were found to be rich in the serum factor obtained through the use of DEAE-cellulose DE-52 and containing the active component of the complement (C4). To test the sensitivity and specificity of the above reagents, components C3 and C5 were purified. After this procedure these components emerged as hemolytically active, electrophoretically and immunophoretically homogeneous components, C3 and C5. DEAE-cellulose DE-52, DEAE-Sephacel, Hydroxylapatite and Ultra-gel AcA-34 were used consecutively as purification agents. The activity yields of components C3 and C5 with regard to the initial serum levels were 31% and 18%, respectively.

Chromatography, Gel↗

PubMed1969

Structural polymorphism of the fourth component of human complement.

The fourth component of human complement (C4) in 102 individual plasma samples has been examined by the technique of antigen-antibody crossed electrophoresis (AACE). Electrophoretic heterogeneity of C4 was manifested by the repeated occurrence of seven different precipitin patterns. These patterns were formed by varying combinations of three subtypes of C4, differing in electrophoretic mobility. The subtypes were designated C, A, and A(1), in order of increasing electrophoretic mobility toward the anode. The evidence that the observed electrophoretic heterogeneity of the C4 molecule represents structural polymorphism rests on five points: the pattern obtained from the plasma of a given individual was reproducible in different runs and with different bleedings; all seven patterns could be demonstrated on the same electrophoretic run; C4 of a given subtype retained its characteristic mobility after purification, when run alone or mixed with plasma containing C4 of other subtypes; the subtypes A(1) and C comprising pattern 6 could be separated chromatographically as well as electrophoretically; and the characteristic relative mobilities of different C4 subtypes, in plasma or after purification, were retained even after the rather large shift in mobility associated with conversion to C4i. The ratio of C4 hemolytic activity to protein concentration varied according to the subtype composition of individual samples, with highest ratios occurring with patterns composed of subtype C alone, intermediate values with patterns consisting of A and C, and lower values occurring with patterns containing subtype A alone. Although the mechanism of inheritance of this polymorphism is not yet clear, the data suggest that subtypes A and A(1) are inherited as autosomal codominant characteristics, independent of the inheritance of subtype C.

Animals↗

PubMed2006

Ficolin-2 recognizes DNA and participates in the clearance of dying host cells.

Ficolin-2 is a serum opsonin, which has been shown to be a pattern recognition molecule in the lectin complement activation pathway. Because innate immune mechanisms are involved in maintaining tissue homeostasis we hypothesized that Ficolin-2 also participate in the clearance of dying host cells. We found that Ficolin-2 binds to late apoptotic cells, as well as to apoptotic bodies and necrotic cells, but not to early apoptotic cells. We demonstrated that Ficolin-2 binds DNA in a calcium dependent manner and that DNA inhibits the binding to late apoptotic and necrotic cells, suggesting that DNA on permeable dying cells is a plausible ligand. Reconstituting serum deficient of Ficolin-2, C1q and mannose-binding lectin with Ficolin-2 augmented deposition of complement C4 on necrotic cells. Opsonization leads to an enhanced attachment/uptake of necrotic cells by macrophages. In conclusion dying host cells expose ligands with the capacity of binding Ficolin-2, which in turn leads to increased attachment and engulfment. Binding of Ficolin-2 to DNA points at nucleic acid exposed by permeable late apoptotic and necrotic cells as one of the ligands for Ficolin-2. Ficolin-2 may therefore be a scavenger molecule participating in the removal of host cells and maintenance of tissue homeostasis.

Animals↗