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1.
Clin Chem Lab Med ; 62(5): 830-834, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-37852014

ABSTRACT

The indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) is still considered the reference method to detect anti-nuclear antibodies (ANA) because of its high sensitivity and represents a relevant tool for the diagnosis of autoimmune rheumatic diseases. During the last decade, the International Consensus on ANA Patterns (ICAP) initiative promoted harmonization and understanding of HEp-2 IFA staining pattern nomenclature, as well as promoting their use in patient care by providing interpretation for HEp-2 IFA test results. In conjunction with a nationwide survey on the evolution of autoantibody diagnostics in autoimmune rheumatic diseases, we focused on the adherence of the Italian laboratories to the ICAP nomenclature analyzing its lights and shadows. The recent ICAP-oriented report, largely used today among Italian laboratories, also represents a further step in harmonizing and improving communication with the clinicians, adding value to laboratory findings and helping with critical clinical decisions.


Subject(s)
Autoimmune Diseases , Rheumatic Diseases , Humans , Laboratories, Clinical , Consensus , Antibodies, Antinuclear , Autoimmune Diseases/diagnosis , Fluorescent Antibody Technique, Indirect/methods , Italy
2.
Clin Chem Lab Med ; 61(7): 1167-1198, 2023 06 27.
Article in English | MEDLINE | ID: mdl-36989417

ABSTRACT

OBJECTIVES: Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA). METHODS: A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "Autoimmunity Testing"; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP). RESULTS: In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations. CONCLUSIONS: These recommendations are an important step to achieve high quality ANA testing.


Subject(s)
Antibodies, Antinuclear , Autoimmune Diseases , Humans , Autoimmune Diseases/diagnosis , Fluorescent Antibody Technique, Indirect/methods , Reference Standards , Cell Line, Tumor
3.
Diagnostics (Basel) ; 13(2)2023 Jan 07.
Article in English | MEDLINE | ID: mdl-36673033

ABSTRACT

The monospecific dense fine speckled (DFS) immunofluorescence assay (IFA) pattern is considered a potential marker to aid in exclusion of antinuclear antibody (ANA)-associated rheumatic diseases (AARD). This pattern is typically produced by autoantibodies against transcription co-activator DFS70/LEDGFp75, which are frequently found in healthy individuals and patients with miscellaneous inflammatory conditions. In AARD patients, these antibodies usually co-exist with disease-associated ANAs. Previous studies reported the occurrence of monospecific autoantibodies that generate a DFS-like or pseudo-DFS IFA pattern but do not react with DFS70/LEDGFp75. We characterized this pattern using confocal microscopy and immunoblotting. The target antigen associated with this pattern partially co-localized with DFS70/LEDGFp75 and its interacting partners H3K36me2, an active chromatin marker, and MLL, a transcription factor, in HEp-2 cells, suggesting a role in transcription. Immunoblotting did not reveal a common protein band immunoreactive with antibodies producing the pseudo-DFS pattern, suggesting they may recognize diverse proteins or conformational epitopes. Given the subjectivity of the HEp-2 IFA test, the awareness of pseudo-DFS autoantibodies reinforces recommendations for confirmatory testing when reporting patient antibodies producing a putative DFS pattern in a clinical setting. Future studies should focus on defining the potential diagnostic utility of the pseudo-DFS pattern and its associated antigen(s).

5.
J Appl Lab Med ; 7(1): 322-330, 2022 01 05.
Article in English | MEDLINE | ID: mdl-34996073

ABSTRACT

The establishment of the International Consensus on ANA Patterns (ICAP) in 2014-2015 was welcomed by members of the medical community as a significant improvement in guiding harmonization of ANA test interpretation and reporting. In the subsequent years, several itinerant meetings and continuous interaction with the community contributed to disseminate the ICAP harmonization on the immunofluorescence patterns observed in the indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) and to promote progressive improvement in the classification of HEp-2 IFA patterns. The 6th ICAP Workshop was held in person on September 6, 2021 as a satellite meeting of the 15th Dresden Symposium on Autoantibodies. This article summarizes the major discussions at the meeting as well as outlining the current plans for the ICAP committee.


Subject(s)
Antibodies, Antinuclear , Autoimmune Diseases , Autoantibodies , Consensus , Fluorescent Antibody Technique, Indirect , Humans
6.
Front Immunol ; 12: 730102, 2021.
Article in English | MEDLINE | ID: mdl-34675922

ABSTRACT

Introduction: The morphological patterns in indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) reflect the autoantibodies in the sample. The International Consensus on ANA Patterns (ICAP) classifies 30 relevant patterns (AC-0 to AC-29). AC-4 (fine speckled nuclear pattern) is associated to anti-SS-A/Ro, anti-SS-B/La, and several autoantibodies. Anti-SS-A/Ro samples may contain antibodies to Ro60 and Ro52. A variation of AC-4 (herein designated AC-4a), characterized by myriad discrete nuclear speckles, was reported to be associated with anti-SS-A/Ro. The plain fine speckled pattern (herein designated AC-4b) seldom was associated with anti-SS-A/Ro. This study reports the experience of four expert laboratories on AC-4a and AC-4b. Methods: Anti-Ro60 monoclonal antibody A7 was used to investigate the HEp-2 IFA pattern. Records containing concomitant HEp-2 IFA and SS-A/Ro tests from Durand Laboratory, Argentina (n = 383) and Fleury Laboratory, Brazil (n = 144,471) were analyzed for associations between HEp-2 IFA patterns and disease-associated autoantibodies (DAA): double-stranded DNA, Scl-70, nucleosome, SS-B/La, Sm, and U1-RNP. A total of 381 samples from Dresden Technical University (TU-Dresden), Germany, were assayed for HEp-2 IFA and DAA. Results: Monoclonal A7 recognized Ro60 in Western blot and immunoprecipitation, and yielded the AC-4a pattern on HEp-2 IFA. Analyses from Durand Laboratory and Fleury Laboratory yielded compatible results: AC-4a was less frequent (8.9% and 2.7%, respectively) than AC-4b (26.1% and 24.2%) in HEp-2 IFA-positive samples. Reactivity to SS-A/Ro occurred in 67.6% and 96.3% of AC-4a-pattern samples against 23% and 6.8% of AC-4b pattern samples. Reciprocally, AC-4a occurred in 24% and 47.1% of anti-SS-A/Ro-positive samples, and in 3.8% and 0.1% of anti-SS-A/Ro-negative samples. Data from TU-Dresden show that the AC-4a pattern occurred in 69% of 169 anti-SS-A/Ro-monospecific samples (62% of all anti-SS-A/Ro-positive samples) and in 4% of anti-SS-A/Ro-negative samples, whereas anti-SS-A/Ro occurred in 98.3% of AC-4a samples and in 47.9% of AC-4b samples. In all laboratories, coexistence of anti-SS-B/La, but not other DAA, in anti-SS-A/Ro-positive samples did not disturb the AC-4a pattern. AC-4a was predominantly associated with anti-Ro60 antibodies. Conclusions: This study confirms the association of AC-4a pattern and anti-SS-A/Ro in opposition to the AC-4b pattern. The results of four international expert laboratories support the worldwide applicability of these AC-4 pattern variants and their incorporation into ICAP classification under codes AC-4a and AC-4b, respectively. The AC-4 pattern should be maintained as an umbrella pattern for cases in which one cannot discriminate AC-4a and AC-4b patterns. The acknowledgment of the AC-4a pattern should add value to HEp-2 IFA interpretation.


Subject(s)
Antibodies, Antinuclear/analysis , Autoantigens/immunology , Autoimmune Diseases/diagnosis , Cell Nucleus/immunology , Fluorescent Antibody Technique, Indirect , RNA, Small Cytoplasmic/immunology , Ribonucleoproteins/immunology , Antibodies, Monoclonal/immunology , Antibody Specificity , Argentina , Autoimmune Diseases/immunology , Brazil , Cell Line , Consensus , Florida , Germany , Humans , Observer Variation , Predictive Value of Tests , Reproducibility of Results
7.
Immunol Res ; 69(6): 594-608, 2021 12.
Article in English | MEDLINE | ID: mdl-34625914

ABSTRACT

Results of the anti-nuclear antibodies-indirect immunofluorescence assay (anti-cell antibodies test) on HEp-2 cell substrates should be communicated to clinicians in a standardized way, adding value to laboratory findings and helping with critical clinical decisions. This paper proposes a test report based on the practices informed by 118 laboratories in 68 countries, with recommendations from the International Consensus on ANA Patterns (ICAP) group. Major focus is placed on the report format containing endpoint titers, immunofluorescence patterns together with anti-cell (AC) nomenclature, remarks on follow-up or reflex testing, and possible other autoantibody associations. ISO 15,189 directives were integrated into the test report. Special situations addressed include serum screening dilutions and endpoint titers, relevance of immunofluorescence patterns with special attention to cytoplasmic patterns, mixed and compound patterns, and how to report different titers corresponding to multiple patterns or autoantibodies in the same sample. This paper suggests a subtitle for the HEp-2-IIFA, namely anti-cell antibodies test, which could gradually substitute the original outdated ANA nomenclature. This ICAP pro forma report represents a further step in harmonizing the way relevant clinical information could be provided by laboratories.


Subject(s)
Antibodies, Antinuclear/immunology , Autoimmune Diseases/immunology , Cell Line , Consensus , Fluorescent Antibody Technique, Indirect , Humans , Practice Guidelines as Topic
8.
BMJ ; 372: n84, 2021 01 20.
Article in English | MEDLINE | ID: mdl-33472855

ABSTRACT

OBJECTIVE: To determine whether tocilizumab improves clinical outcomes for patients with severe or critical coronavirus disease 2019 (covid-19). DESIGN: Randomised, open label trial. SETTING: Nine hospitals in Brazil, 8 May to 17 July 2020. PARTICIPANTS: Adults with confirmed covid-19 who were receiving supplemental oxygen or mechanical ventilation and had abnormal levels of at least two serum biomarkers (C reactive protein, D dimer, lactate dehydrogenase, or ferritin). The data monitoring committee recommended stopping the trial early, after 129 patients had been enrolled, because of an increased number of deaths at 15 days in the tocilizumab group. INTERVENTIONS: Tocilizumab (single intravenous infusion of 8 mg/kg) plus standard care (n=65) versus standard care alone (n=64). MAIN OUTCOME MEASURE: The primary outcome, clinical status measured at 15 days using a seven level ordinal scale, was analysed as a composite of death or mechanical ventilation because the assumption of odds proportionality was not met. RESULTS: A total of 129 patients were enrolled (mean age 57 (SD 14) years; 68% men) and all completed follow-up. All patients in the tocilizumab group and two in the standard care group received tocilizumab. 18 of 65 (28%) patients in the tocilizumab group and 13 of 64 (20%) in the standard care group were receiving mechanical ventilation or died at day 15 (odds ratio 1.54, 95% confidence interval 0.66 to 3.66; P=0.32). Death at 15 days occurred in 11 (17%) patients in the tocilizumab group compared with 2 (3%) in the standard care group (odds ratio 6.42, 95% confidence interval 1.59 to 43.2). Adverse events were reported in 29 of 67 (43%) patients who received tocilizumab and 21 of 62 (34%) who did not receive tocilizumab. CONCLUSIONS: In patients with severe or critical covid-19, tocilizumab plus standard care was not superior to standard care alone in improving clinical outcomes at 15 days, and it might increase mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT04403685.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , COVID-19 Drug Treatment , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/mortality , COVID-19/therapy , Critical Illness , Female , Follow-Up Studies , Hospitalization , Humans , Infusions, Intravenous , Male , Middle Aged , Respiration, Artificial , Severity of Illness Index , Treatment Outcome , Young Adult
9.
Front Immunol ; 11: 586558, 2020.
Article in English | MEDLINE | ID: mdl-33193413

ABSTRACT

Behçet´s disease (BD) is a heterogeneous condition consisting of idiopathic systemic vasculitis affecting large and small blood vessels of different types (i.e., arteries, veins, or capillaries). The disease frequently occurs in young adults without gender predilection, differently from several other autoimmune conditions. This challenging illness has recently been proposed by some authors as an example of complex autoinflammatory syndrome. Although much remains unanswered about BD pathogenesis, recent understanding of some aspects of innate immunity have clarified a few issues (and raised others). HLA-B*51 represents the strongest genetic risk factor for BD to date, albeit several other HLA-independent loci have also been associated with the disease. The consistent hyper-reactivity against Streptococcus sanguinis antigens and alterations in oral and gut microbioma suggests that infectious agents may play an important role. Moreover, functional abnormalities of pattern recognition receptors, especially Toll-like receptors in monocytes, have been demonstrated in patients with BD and can be associated with the development of the disease. Neutrophil hyperactivity is one of the most consistent findings in BD pathogenesis, as demonstrated by exacerbated constitutive oxidative burst, chemotaxis and NET formation. However, some studies suggest that the phagocyte-activated status in BD is not primary to the disease itself, but rather restricted to a fraction of patients with severe disease activity, and probably secondary to activating soluble factors carried by serum/plasma from BD patients. Herein we review the state of the art on BD etiopathogenesis with special emphasis on the participation of the innate immune system.


Subject(s)
Behcet Syndrome/immunology , Immunity, Innate/immunology , Humans , Risk Factors
10.
Clin Chem Lab Med ; 59(1): 197-207, 2020 08 10.
Article in English | MEDLINE | ID: mdl-32776893

ABSTRACT

Objectives: Reference materials are important in the standardization of autoantibody testing and only a few are freely available for many known autoantibodies. Our goal was to develop three reference materials for antibodies to PML bodies/multiple nuclear dots (MND), antibodies to GW bodies (GWB), and antibodies to the nuclear mitotic apparatus (NuMA). Methods: Reference materials for identifying autoantibodies to MND (MND-REF), GWB (GWB-REF), and NuMA (NuMA-REF) were obtained from three donors and validated independently by seven laboratories. The sera were characterized using indirect immunofluorescence assay (IFA) on HEp-2 cell substrates including two-color immunofluorescence using antigen-specific markers, western blot (WB), immunoprecipitation (IP), line immunoassay (LIA), addressable laser bead immunoassay (ALBIA), enzyme-linked immunosorbent assay (ELISA), and immunoprecipitation-mass spectrometry (IP-MS). Results: MND-REF stained 6-20 discrete nuclear dots that colocalized with PML bodies. Antibodies to Sp100 and PML were detected by LIA and antibodies to Sp100 were also detected by ELISA. GWB-REF stained discrete cytoplasmic dots in interphase cells, which were confirmed to be GWB using two-color immunofluorescence. Anti-Ge-1 antibodies were identified in GWB-REF by ALBIA, IP, and IP-MS. All reference materials produced patterns at dilutions of 1:160 or greater. NuMA-REF produced fine speckled nuclear staining in interphase cells and staining of spindle fibers and spindle poles. The presence of antibodies to NuMA was verified by IP, WB, ALBIA, and IP-MS. Conclusions: MND-REF, GWB-REF, and NuMA-REF are suitable reference materials for the corresponding antinuclear antibodies staining patterns and will be accessible to qualified laboratories.


Subject(s)
Antibodies, Antinuclear/immunology , Cell Cycle Proteins/blood , Cellular Structures , Immunoassay/standards , Nuclear Proteins/blood , Cell Cycle Proteins/immunology , Cell Line, Tumor , Cellular Structures/immunology , Humans , Nuclear Proteins/immunology , Reference Standards
11.
Pigment Cell Melanoma Res ; 33(3): 490-497, 2020 05.
Article in English | MEDLINE | ID: mdl-31883196

ABSTRACT

Acral lentiginous melanoma (ALM) is a rare subtype of melanoma with aggressive behavior. IMPDH enzyme, involved in de novo GTP biosynthesis, has been reported to assemble into large filamentary structures called rods/rings (RR) or cytoophidium (cellular snakes). RR assembly induces a hyperactive state in IMPDH, usually to supply a high demand for GTP nucleotides, such as in highly proliferative cells. We investigate whether aggressive melanoma tumor cells present IMPDH-based RR structures. Forty-five ALM paraffin-embedded tissue samples and 59 melanocytic nevi were probed with anti-IMPDH2 antibody. Both the rod- and ring-shaped RR could be observed, with higher frequency in ALM. ROC curve analyzing the proportions of RR-positive cells in ALM versus nevi yielded a 0.88 AUC. Using the cutoff of 5.5% RR-positive cells, there was a sensitivity of 80% and specificity of 85% for ALM diagnosis. In ALM, 36 (80%) showed RR frequency above the cutoff, being classified as RR-positive, compared with only 9 (15%) of the nevi (p < .001). Histopathology showed that 71% of the RR-positive specimens presented Breslow thickness > 4.0mm, compared with only 29% in the RR-low/negative (p = .039). We propose that screening for RR structures in biopsy specimens may be a valuable tool helping differentiate ALM from nevi and accessing tumor malignancy.


Subject(s)
IMP Dehydrogenase/metabolism , Melanoma/enzymology , Melanoma/pathology , Genetic Heterogeneity , Humans , Nevus, Pigmented/pathology
12.
Ann Hepatol ; 18(5): 685-692, 2019.
Article in English | MEDLINE | ID: mdl-31167733

ABSTRACT

INTRODUCTION AND OBJECTIVES: Cryoglobulinemia is one of the most frequent extrahepatic manifestations of chronic hepatitis C virus (HCV) infection and it may evolve to cryoglobulinemic vasculitis (CryoVas) which is a systemic vasculitis that affects small-sized vessels. The objective of this study was to evaluate the prevalence of cryoglobulinemia and CryoVas in HCV patients in São Paulo, Brazil. MATERIALS AND METHODS: A cross-sectional study was conducted and included sixty-eight viremic HCV patients, without HIV or hepatitis B coinfection. A thorough clinical and laboratory evaluation was performed including the detection of serum cryoglobulins and measurement of serum complement components. The classification criteria for CryoVas were applied. RESULTS: The study population comprised mainly women (61.8%) with long term HCV infection (median 11.0 years). Advanced hepatic fibrosis was detected in 20.6% (14/68) of cases. Cryoglobulins were detected in 48.5% (33/68) of HCV-patients with type III cryoglobulinemia being the most frequent. CryoVas was present in 10.3% (7/68) and the main manifestations were peripheral neuropathy (85.7%), palpable purpura (42.8%), arthralgias (42.8%) and renal involvement (42.8%). Life-threatening manifestations were rare. Low hemolytic C2, C4 and total hemolytic complement (CH100) levels were common findings in the cryoglobulinemia group. Low C4 levels were independently associated with the development of CryoVas. CONCLUSION: A high prevalence of cryoglobulinemia and CryoVas was found in Brazilian HCV-patients. CryoVas patients mostly presented non-life-threatening manifestations, especially peripheral neuropathy. Complement abnormalities were common in patients with cryoglobulinemia and low serum C4 levels were associated with CryoVas.


Subject(s)
Cryoglobulinemia/epidemiology , Hepatitis C, Chronic/complications , Vasculitis/epidemiology , Adult , Aged , Brazil/epidemiology , Complement System Proteins/metabolism , Cross-Sectional Studies , Cryoglobulinemia/etiology , Cryoglobulinemia/metabolism , Female , Hepatitis C, Chronic/metabolism , Humans , Male , Middle Aged , Prevalence , Prognosis , Retrospective Studies , Vasculitis/etiology , Vasculitis/metabolism
13.
Clin Chem Lab Med ; 57(11): 1754-1763, 2019 Oct 25.
Article in English | MEDLINE | ID: mdl-31005948

ABSTRACT

Background International autoantibody standards, traditionally based on material obtained from plasmapheresis of single subjects, represent individual immune response and may not comprehend the heterogeneity of the general population. The anti-DFS70 autoantibody yields a characteristic dense fine speckled (DFS) nuclear pattern on indirect immunofluorescence assay on HEp-2 cells (HEp-2 IFA) and speaks against autoimmunity. We propose a novel strategy for developing autoantibody reference standards, based on stepwise pooling of serum samples from hundreds of individuals with anti-DFS70 antibodies. Methods Within a 2-year period, serum samples were selected from routine HEp-2 IFA according to the following criteria: DFS HEp-2 IFA pattern at titer ≥1:640; anti-DFS70 reactivity in three analyte-specific tests (Western blot [WB], enzyme-linked immunosorbent assay [ELISA] and chemiluminescent immunoassay [CLIA]). Aliquots of individual samples were combined into progressively larger pools with stepwise validation of intermediary pools as for individual samples. Validated intermediary pools were merged into a final pool for lyophilization. Results A total of 741 validated samples yielded a 750 mL final pool that was lyophilized into thousands of 200 µL-aliquots. Reconstituted aliquots yielded the expected anti-DFS70 reactivity in ELISA, CLIA and WB, as well as high-titer DFS HEp-2 IFA pattern. The appropriate anti-DFS70 reactivity of the lyophilized pool was confirmed by seven international expert centers, using HEp-2 IFA, ELISA, WB and immunoprecipitation. Conclusions This proof-of-concept study provides an innovative and efficient strategy to build serum reference standards for autoantibody testing. The anti-DFS70 standard will integrate the panel of standards of Autoantibody Standardization Committee (ASC, www.autoab.org), contributing to education for proper assay validation and interpretation of the DFS pattern and other HEp-2 IFA patterns.


Subject(s)
Adaptor Proteins, Signal Transducing/immunology , Autoantibodies/metabolism , Mass Spectrometry/methods , Proof of Concept Study , Female , Humans , Male
15.
Expert Rev Clin Immunol ; 15(3): 241-250, 2019 03.
Article in English | MEDLINE | ID: mdl-30623687

ABSTRACT

INTRODUCTION: Anti-DFS70 antibodies and their clinical associations remain an immunological paradox. Unlike other antinuclear antibodies (ANA), there is a growing body of evidence that anti-DFS70 antibodies, when present in high titers and in isolation (without accompanying other antibodies), are useful to aid in the exclusion of ANA associated rheumatic diseases. Areas covered: This review aims to analyze and interpret the current published knowledge and recent findings to provide guidance in the use of anti-DFS70 antibodies to analyze associations of this unique autoantibody. Expert commentary: Although the association of anti-DFS70 antibodies is still unknown, their use as a biomarker that can aid in the exclusion of ANA related diseases is well-established.


Subject(s)
Adaptor Proteins, Signal Transducing/immunology , Antibodies, Antinuclear/immunology , Rheumatic Diseases/immunology , Transcription Factors/immunology , Autoantigens/immunology , Biomarkers/analysis , Humans
20.
APMIS ; 125(10): 902-909, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28929596

ABSTRACT

This study investigated phenotypic and functional characteristics of lymphocytes in children with common variable immunodeficiency (CVID) and unclassified hypogammaglobulinemia (UH), as well as B-cell subsets in non-consanguineous parents. Blood samples of 30 children, CVID (n = 9), UH (n = 9), healthy donors HD (n = 12), and 19 adults (parents and controls) were labeled by a combination of surface markers to identify CD4, CD8 T-cell and B-cell subpopulations. T-cell cytokine production in children was analyzed in vitro after stimulation with phytohemagglutinin (PHA) and tetanus toxoid. We observed low percentages of switched memory B cells in children with CVID, increase in total CD4+ T-cell counts, and high percentages of transitional B cells only in UH group. Analysis of T-cell immunity showed that CVID children had decreased percentages of CD8+ IFN-γ-producing cells after stimulation with PHA and tetanus toxoid. Parent of children with CVID had low percentages of naive B cell and increased percentages of memory B cells in comparison with controls. These results suggest that (i) early combined immune defect in children with CVID and (ii) a possible familial B-cell disturbance in pediatric CVID.


Subject(s)
B-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Common Variable Immunodeficiency/pathology , Adolescent , Adult , Child , Child, Preschool , Cytokines/metabolism , Female , Humans , Immunologic Factors , Male , Middle Aged , Phytohemagglutinins/immunology , Tetanus Toxoid/immunology
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