Immune Deficiency In Patients Research Articles

Association of immune deficiency with prognosis and corticosteroid treatment benefits among patients with acute respiratory distress syndrome.

The role of corticosteroids in acute respiratory distress syndrome (ARDS) remains contentious. This study aims to investigate the prognostic significance of immune deficiency in patients with ARDS and its response to varying doses of corticosteroids. This single-center, retrospective cohort study enrolled 657 ARDS patients from January 24, 2008, to September 12, 2022, at Zhongshan Hospital of Fudan University, Shanghai, China. The patients were categorized into a discovery dataset (n=357) and a validation dataset (n=300), based on admission date. Further validation of the results in the validation dataset was used to enhance the credibility of the study conclusions. The study examined the association between immune deficiency and the patients' clinical characteristics, treatment measures, and prognosis. The primary outcome was 28-day mortality post disease onset. Data analysis was conducted from June 15, 2023 to August 15, 2023. The initial risk factor analysis in the discovery dataset was primarily based on the clinical characteristics, and the results suggested that immune deficiency likely impacted overall survival among patients receiving different doses of corticosteroid treatment. Multivariate analysis identified immune deficiency as an independent prognostic factor for overall survival in both the discovery and validation datasets. The final analysis revealed that patients with mild to moderate ARDS [discovery dataset: hazard ratio (HR) =1.719; 95% confidence interval (CI): 1.229-2.406; log-rank test P=0.001; validation dataset: HR =1.874; 95% CI: 1.238-2.837; log-rank test P=0.002] or severe ARDS (discovery dataset: HR =1.874; 95% CI: 1.007-3.488; log-rank test P=0.04; validation dataset: HR =1.698; 95% CI: 1.042-2.768; log-rank test P=0.03) with immune deficiency exhibited lower overall survival rates. Patients with mild to moderate ARDS and immune deficiency showed greater benefits from low-dose corticosteroid treatment (HR =0.409; 95% CI: 0.249-0.671; P<0.001 for interaction), whereas those with severe ARDS and immune deficiency benefitted from both low and high-dose treatments (low corticosteroid: HR =0.299; 95% CI: 0.136-0.654; high corticosteroid: HR =0.458; 95% CI: 0.214-0.981; P=0.005 for interaction). Immune deficiency is an independent risk factor in ARDS. Incorporating it into the disease severity grading system based on the Berlin criteria may enhance personalized treatment approaches for ARDS patients. These findings warrant further validation through prospective, large-scale, multicenter randomized controlled trials (RCTs).

462 Gametocyte Specific Factor 1 contributes to the Th phenotype in Cutaneous T-Cell Lymphomas

Ectopic expression of Gametocyte Specific Factor 1 (GTSF1) in Cutaneous T-Cell Lymphoma (CTCL) patients has been reported by several groups. Moreover, it has been associated with a worse prognosis and late-stage CTCL. GTSF1 is a gamete gene that participates in the piRNA pathway to silence retrotransposons on the genome. Despite the established association with a worse prognosis the molecular function of GTSF1 expression remains unknown. Therefore, we established shRNA-mediated GTSF1 knockdown CTCL cell lines. Using qRT-PCR, Western blot and a retrotransposition assay, we demonstrated that GTSF1 knockdown does not lead to mobilization of the retrotransposon LINE-1. These data suggest GTSF1 has a novel role in CTCL. Interestingly, after GTSF1 knockdown in the Mac2A cell line, we observed striking growth inhibition, suggesting this gene is a key player in CTCL carcinogenesis. To further explore this role, we performed RNA-Seq, comparing GTSF1 knockdown to control cells. Differential gene expression analysis using DESeq2, revealed 12496 differentially expressed genes (p adjusted <0.05). Pathway enrichment analysis was performed via GO, KEGG, Reactome and WikiPathways. We observed an enrichment of several pathways including response to stimulus, immune response, response to cytokine and inflammatory response. More specifically, transcriptome analysis showed an increased expression of cytokine induced genes, such as XAF1, IFI27 and IFI44L, and genes associated with a Th1 phenotype, IFNG and TNF. Research shows that CTCL progression leads to defects in Th1 cytokine production (IFN-γ and TNF-α) by antitumor immune cells and an enhanced Th2 cytokine production (IL-4 and IL-5) by malignant T cells. The chronic production of Th2 cytokines by malignant cells leads to immune deficiency in patients, allowing malignant cells to proliferate and the disease to progress. Taken together, these data suggest GTSF1 as a novel regulator of the Th phenotype on CTCL, thereby placing it as a potential treatment target for regulating disease progression.

T-Cell Progenitors As A New Immunotherapy to Bypass Hurdles of Allogeneic Hematopoietic Stem Cell Transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is the treatment of preference for numerous malignant and non-malignant hemopathies. The outcome of this approach is significantly hampered by not only graft-versus-host disease (GvHD), but also infections and relapses that may occur because of persistent T-cell immunodeficiency following transplantation. Reconstitution of a functional T-cell repertoire can take more than 1 year. Thus, the major challenge in the management of allogeneic HSCT relies on the possibility of shortening the window of immune deficiency through the acceleration of T-cell recovery, with diverse, self-tolerant, and naïve T cells resulting from de novo thymopoiesis from the donor cells. In this context, adoptive transfer of cell populations that can give rise to mature T cells faster than HSCs while maintaining a safety profile compatible with clinical use is of major interest. In this review, we summarize current advances in the characterization of thymus seeding progenitors, and their ex vivo generated counterparts, T-cell progenitors. Transplantation of the latter has been identified as a worthwhile approach to shorten the period of immune deficiency in patients following allogeneic HSCT, and to fulfill the clinical objective of reducing morbimortality due to infections and relapses. We further discuss current opportunities for T-cell progenitor-based therapy manufacturing, including iPSC cell sources and off-the-shelf strategies. These opportunities will be analyzed in the light of results from ongoing clinical studies involving T-cell progenitors.

Update of the mechanism and characteristics of tuberculosis in chronic kidney disease : Review article.

The risk of tuberculosis (TB) is significantly increased in patients with chronic kidney disease (CKD), which is closely related to hyperparathyroidism, malnutrition and oxidative stress as well as immune deficiency in patients with end-stage renal disease (ESRD). VitaminD deficiency and gender bias are independent risk factors. In the TB screening and diagnosis test of CKD, interferon-gamma release assays (IGRA), including T‑SPOT.TB test (T-SPOT) and QuantiFERON-TB Gold In-Tube (QFT-GIT) have been available. Many studies have found that they are more sensitive and specific than tuberculin skin test (TST). At present, IGRA has been used to study various types of immunocompromised patients. For CKD patients with TB, the choice and dosage of anti-TB drugs need to be reconsidered. Weekly treatment with rifapentin (RFT) and isoniazid (INH) for 3 months is an effective treatment for latent tuberculosis infection (LTBI) in hemodialysis (HD) patients. Therefore, in this review we discuss CKD and TB, its pathogenesis, clinical features, diagnosis and treatment advancements.

Clinical and immunological assessment of children with ataxia telangiectasia attending Sohag university hospital in Upper Egypt

Ataxia Telangiectasia (AT) is a very rare autosomal recessive primary immune deficiency (PID) disease that affects 1 in 10,000-40,000 new births per year in the world. It is caused by biallelic mutations in ataxia telangiectasia mutated (ATM) gene and characterized by a progressive cerebellar ataxia. The clinical profile of AT children in Upper Egypt in missing. Herein, we evaluated the clinical characteristics and immunological profiles of patients with AT attending Sohag University Hospital. This was a cross-sectional study, included 21 AT patients attending the Neurological and Immunological Units, Pediatric Department, Sohag University Hospital, starting April 2018 to the end of March 2019. AT represented 20.5% of all PID patients attending the hospital. The most common type of humoral immune deficiency in patients with AT was specific IgA deficiency (52.3%) followed by hypogammaglobulinemia (23.8%). Recurrent sinopulmonary infection with different degrees of severity was the common immunological problem. The most common neurological manifestations in our studied patients, other than the ataxia, were language delay and eye movement abnormalities followed by developmental delay and head nodding. None of our patients had developed malignancy till the end of the study.

Features of the immune status in chronic hepatitis C in patients with lymphopriliferative diseases

Tumor transformation of immunocompetent cells in patients with chronic lymphoproliferative diseases (CLPD) leads to the formation of secondary immune deficiency, which increases the prevalence of infectious complications. Whether the presence of hepatitis C virus (HCV) and the formation of chronic hepatitis (HCV) further weaken the immunoreactivity of the patient, remains poorly understood. The purpose of this work was to reveal the patterns of HCG formation in patients with CLPD with a detailed analysis of immune disorders associated with the chronicity of viral hepatitis C. Another aim of the study was to disclose the patterns of HCG formation in patients with CLP with a detailed analysis of immune disorders associated with the chronicity of viral hepatitis C. The comparative assessment of immunological and biochemical parameters was carried out in 110 patients with HCV (85 – chronic lymphocytic leukemia, 25 – non- Hodgkin lymphoma), with the presence of hepatitis C virus markers (n=20) and 90 patients negative for HCV. To identify intergroup differences, the method of nonparametric statistics was used: the Mann-Whitney criterion. Results. It was found that the group of HCV-infected patients is represented by younger persons compared to uninfected patients (median age – 44 years vs. 60 years, p=0.004). Analyzing the state of the immune system, we have revealed that regardless of the presence of chronic hepatitis C, all patients had a defect in both cellular and humoral immunity. The degree of immune deficiency did not have a direct dependence on viral liver damage. Moreover, in the presence of HCV infection, there was an increase in the microbicidal activity of neutrophils, as well as an increase in the expression of CD95+ on lymphoid cells. Cytokine levels during HCV contamination fluctuated in different directions. There was an increase in the level of ALT in the group of patients with HCV. Findings. The formation of immune deficiency in patients with CLPD is largely associated with the presence of oncopathology and practically does not depend on the presence of chronic hepatitis C.

Humoral Immunodeficiency and Immune Globulin Replacement Therapy (IGRT) Usage in DiGeorge Syndrome.

An analysis of patients in the United States Immunodeficiency Network (USIDNET) registry previously described a discordance in the reported prevalence of humoral immune deficiency in patients with DiGeorge syndrome (DGS) and its treatment. The primary purpose of this study is to evaluate the rates of humoral immunodeficiency and immune globulin replacement therapy (IGRT) use in patients with DiGeorge syndrome in the USIDNET registry as of September 2016, and to correlate IGRT use with prior infections and laboratory evidence of immune deficiency. Current patients in the USIDNET registry with DGS were identified. Patients who were treated with immune globulin replacement therapy (IGRT) were compared with those who were untreated with respect to their laboratory findings and clinical history. Four hundred seventy-three patients were identified. The use of IGRT in patients with DGS has increased over time from 3 to 6.6%. IGRT was more common in patients with humoral immune deficiency (18.2% of those with hypogammaglobulinemia, 39.1% of those with documented low vaccine titers), but most patients with evidence of humoral immune deficiency remain untreated with IGRT. Patients treated with IGRT were more likely to have experienced episodes of pneumonia, sepsis, and bacterial skin infections (p < 0.01 for all). Humoral immune deficiencies were more common among patients with DGS than previously reported. IGRT was used most commonly in patients with DGS who demonstrated frequent or severe bacterial infections. There is still a significant deficit between those with DGS who have laboratory evidence of a humoral immune deficiency and those being treated for it.

Evaluation of primary immunodeficiency in patients with meningitis in fever hospitals

Background: The hallmark of primary immunodeficiency diseases is increased susceptibility to recurrent, severe and opportunistic infections. In this study we evaluate patients with meningitis for underlying primary immunodeficiencies.Methods: During the period from August 2016 to February 2017, thirty infant and children patients (16 male and 14 female) with age ranged from 40 days to 15 years participated in the study were admitted to Faqus and Zagazig fever hospitals with meningitis were evaluated for primary immunodeficiencies by measurement of serum immunoglobulin levels, assessment of T-Cell Receptor Excision Circles and assessment of complement system by CH50 assay.Results: This study showed that (50%) had deficient IgG, (20%) had deficient IgA, (30%) hyper IgE, (30%) hyper IgM and 10% Deficient in all Immunoglobulins. The study also showed that (43.3%) of the study group had TREC deficiency, (36.7%) were CH50 deficient and 26.7 had both TREC and CH50 deficiency. Conclusions: Meningitis may be the presenting manifestation of immunodeficiency diseases as there is high incidence of primary immune deficiency in patients with meningitis. TRECS and CH50 are decreased in most cases of meningitis which indicate high percentage of primary immunodeficiency diseases among those patients.

The Prevalence of Immune Deficiency in Patients with Evans Syndrome: A Retrospective Chart Review Study

The Prevalence of Immune Deficiency in Patients with Evans Syndrome: A Retrospective Chart Review Study

Increased susceptibility for aspergillosis and post‐transplant immune deficiency in patients with gene variants of TLR4 after stem cell transplantation

Toll-like receptors (TLRs) detect invading pathogens through several pattern-recognition mechanisms and play a central role in the regulation of the immune system. In allogeneic hematopoietic stem cell transplantation (HSCT), the frequent opportunistic fungal infections remain an important cause of mortality and morbidity in these highly immunocompromised patients. We analyzed 154 patients after allogeneic HSCT for acute leukemia for TLR4 gene variants 1063A/G (D299G) and 1363C/T (T399I) with their respective donors, and correlated the results with the incidence of invasive aspergillosis (IA) infection after transplant. Probable and proven IA in recipients was significantly increased if either recipients or donors exhibited one of the two TLR4 gene variants. In addition, recipients with TLR gene variants and IA showed a delayed T cell and NKT cell immune reconstitution after transplant. Increased susceptibility for IA was not associated with an increased rate of death-in-remission or decreased estimate for overall survival. These findings reinforce the importance of genetic variants in innate immunity and IA among the recipients of allogeneic HSCT.

T-Cells From Patients with CLL Exhibit Phenotypic and Transcription Factor Profiles of Exhaustion Independent of CMV Serostatus

Abstract 1780Cancer is associated with immune dysfunction, contributing to the failure to mount an effective anti-tumor immune response. T-cell exhaustion, a state of acquired T-cell dysfunction initially described in the context of chronic viral infections, has recently been described in human solid tumors. We have previously demonstrated alterations in gene expression and defects in function in T-cells from patients with chronic lymphocytic leukemia (CLL) and noted similarities to those described in exhausted T-cells in murine models. Therefore, we used multiparameter flow cytometry to determine if T-cells from patients with untreated CLL (n=23) had surface phenotypic and transcription factor profiles of exhaustion. When compared with healthy controls (n=10), an increased proportion of circulating CD8+ T-cells showed an effector-memory phenotype (p=0.018), with a shift towards a greater proportion of CCR7-CD45RA+ terminally differentiated cells. We found increased expression of markers of exhaustion including CD279 (PD-1) (p=0.0057), CD160 (p=0.0006), CD244 (p=0.0057), and CD57 (p=0.011), and decreased expression of CD28 (p=0.0058) on CLL CD8+ T-cells compared with healthy CD8+ T-cells. Increased expression of PD-1 (p=0.0019), CD160 (p=0.0011), CD57 (p=0.007), and LAG-3 (p=0.038) was also noted on CLL CD4+ T-cells. We next determined the level of the transcription factors T-bet and eomesodermin and the transcriptional repressor Blimp-1, as these proteins have been implicated in CD8+ effector-memory differentiation and development of T-cell exhaustion. Importantly, CD8+ T-cells from CLL patients showed increased expression of T-bet (p=0.038), eomesodermin (p=0.0037), and Blimp-1 (p=0.0002), compared with CD8+ T-cells from healthy donors. Furthermore, PD-1 expression identified a subset of exhausted CD8+ T-cells with high intranuclear staining of Blimp-1 that was markedly expanded in patients with CLL (p=0.0002).Previous studies have identified expanded populations of CMV specific CD8+ T-cells in CMV seropositive CLL patients. As chronic viral infection is a known cause of T-cell exhaustion, we determined whether our findings were limited to CMV seropositive patients. We observed that increased expression of T-bet and decreased expression of CD28 was seen only in CD8+ T-cells from CMV seropositive patients. T-bet represses expression of PD-1 and sustains CD8+ T-cell responses during chronic viral infection, and we noted relatively lower expression of PD-1 on CD8+ T-cells in seropositive compared with seronegative patients (p=0.049), although PD-1 expression was still higher than in healthy controls. However, CD8+ T-cells from both CMV seronegative and seropositive patients had significantly higher expression of CD160, CD244, and CD57 compared to CD8+ T-cells from healthy donors (Table 1). Furthermore, CD8+ T-cells from both CMV seronegative and seropositive patients had increased expression of Blimp-1 and eomesodermin.Table 1Surface phenotype/transcription factor profile of CLL according to CMV serostatusHealthyCLL: CMV IgG negative (n=8)CLL: CMV IgG positive (n=8)PhenotypePD-1LOWINCREASED**INCREASED*CD160LOWINCREASED**INCREASED**CD57LOWINCREASED*INCREASED**CD244LOWINCREASED*INCREASED***CD28HIGHNO CHANGEDECREASED**Transcription factorT-betLOWNO CHANGEINCREASED**EomesLOWINCREASED*INCREASED***Blimp-1LOWINCREASED***INCREASED****p<0.05,**p<0.01,***p<0.001In conclusion, T-cells from patients with CLL show phenotypic and transcription factor profiles of T-cell exhaustion that is not limited to the CMV-seropositive group. These findings may explain the acquired immune deficiency in patients with CLL, and provide potential therapeutic targets to reverse immune dysfunction in this disease. Disclosures:Gribben:Roche: Honoraria; Celgene: Honoraria; GSK: Honoraria; Mundipharma: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria.

Granulomatous skin lesions complicating Varicella infection in a patient with Rothmund-Thomson syndrome and immune deficiency: case report

Rothmund-Thomson syndrome (RTS)(OMIM 268400) is a rare autosomal recessive genodermatosis characterized by poikiloderma, small stature, skeletal and dental abnormalities, cataract and an increased risk of cancer. It is caused by mutations in RECQL4 at 8q24. Immune deficiency is not described as a classical feature of the disease. Here we report the appearance of granulomatous skin lesions complicating primary Varicella Zoster Virus infection in a toddler with Rothmund Thomson syndrome and immune deficiency. Although granulomatous disorders are sometimes seen after Herpes zoster, they are even more rare after Varicella primary infection. Granulomas have hitherto not been described in Rothmund-Thomson syndrome. With this report we aim to stress the importance of screening for immune deficiency in patients with Rothmund-Thomson syndrome.

CD57+ T lymphocytes and functional immune deficiency

CD57(+) expression in T lymphocytes has been recognized for decades as a marker of in vitro replicative senescence. In recent years, accumulating evidences have pointed on the utility of this marker to measure functional immune deficiency in patients with autoimmune disease, infectious diseases, and cancers. We review here the relevant literature and implications in clinical settings.

Novel mutations in CRAC channel protein Orai1 cause immunodeficiency associated with non-immunological disease (89.23)

Abstract Orai1 has recently been identified as a pore subunit of the Ca2+ release activated Ca2+ (CRAC) channel essential for the function of T lymphocytes, mast cells and other cells types. A point mutation in Orai1 abrogates CRAC channel function and causes Severe Combined Immunodeficiency (SCID) in human infants. We here report that the immunodeficiency is accompanied by hypohidrotic ectodermal dysplasia (HED) and congenital myopathy, characterized by absent sweat production, dysplastic dental enamel, non-progressive muscle weakness and histologically a predominance of type I and atrophic type II mucle fibers. A major defect in the activation of NF-kB, known to cause HED accompanied by immune deficiency in patients with mutations in IkBα or IKKγ, was ruled out, although a partial, Ca2+ dependent impairment of NF-kB activation downstream of TCR crosslinking was observed. An novel nonsense mutation in Orai1 was observed in an unrelated SCID patient causing a premature truncation of Orai1 protein. The resulting lack of Ca2+ influx and CRAC channel activity could be rescued by ectopic expression of Orai1 in the patient’s cells. The immunodeficiency in this patient is accompanied by fatal progressive growth retardation and encephalopathy, but HED and myopathy are absent. These clinical phenotypes indicate that Orai1 may not only be necessary for regulating Ca2+ influx in the immune system but also several other tissues.

Selective antibody immune deficiency in a patient with Smith–Lemli–Opitz syndrome

Smith-Lemli-Opitz syndrome is a rare autosomal recessive disorder characterized by multiple congenital anomalies and various degrees of cognitive deficits. This condition results from a deficiency of 7-dehydrocholesterol reductase, a critical step in cholesterol biosynthesis. Children with Smith-Lemli-Opitz syndrome have frequent infections, particularly of the respiratory tract. Immunodeficiency, however, is not recognized as a part of this metabolic condition. Frequent infections are usually attributed to a decreased patient mobility and reduced respiratory effort secondary to muscular hypotonia and mental retardation, which are often present in affected individuals. We describe a patient with Smith-Lemli-Opitz syndrome and recurrent respiratory infections who was found to have a selective antibody deficiency. The immunological diagnosis was based on an absent immune response to Pneumovax. She also had no immunological response to hepatitis B vaccine and was unable to break down red cells with isoagglutinin B. Therapy with intravenous IgG (IVIG) was initiated. Infections were less severe, although they still occurred in a high frequency after initiation of the IVIG therapy. This finding prompts the need for a higher index of suspicion for an underlying immune deficiency in patients with Smith-Lemli-Opitz syndrome who present with recurrent and chronic infections. Early recognition and appropriate therapeutic interventions may decrease the severity of infections, prevent potentially fatal infections, and eventually improve the quality of life in these patients.

Nosocomial infections and immunity: lesson from brain-injured patients

Of brain-injured patients admitted to intensive care units, a significant number acquires nosocomial infections. Increased susceptibility to infectious agents could, at least partly, be due to transient immunodepression triggered by brain damage. Immune deficiency in patients with severe brain injury primarily involves T cell dysfunction. However, humoral and phagocytic deficiencies are also detectable. Activation of the hypothalamo–pituitary–adrenal axis and the sympathetic nervous system plays a crucial role in brain-mediated immunodepression. In this review we discuss the role of immunodepression in the development of nosocomial infections and clinical trials on immunomodulation in brain-injured patients with hospital-acquired infections.

Possible contribution of circulating interleukin-10 (IL-10) to anti-tumor immunity and prognosis in patients with unresectable hepatocellular carcinoma

Objectives: Interleukin-10 (IL-10) has been implicated in immune deficiency in patients with cancer. The relationship of this cytokine as measured in serum to anti-tumor immunity and prognosis was investigated in unresectable hepatocellular carcinoma. Methods: This study consisted of 74 consecutive patients with unresectable hepatocellular carcinoma (median age, 65 years). Forty-four healthy age-matched subjects and 32 patients with cirrhosis but no carcinoma served as controls. Patients with hepatocellular carcinoma were divided into those with serum IL-10 concentrations above (high group, n=39) or below (low group, n=35) 10 pg/ml. Results: Age, gender, Child–Pugh grade, and tumor stage distributions were similar in high and low groups. The patients of high group showed lower in lymphokine-activated killer (LAK) and natural killer (NK) activities than those of low group ( P<0.01 and 0.01, respectively). Serum IL-10 concentration was a significant factor contributing to low activities of LAK and NK by logistic regression analysis ( P<0.05 and 0.05, respectively). The high group had a significantly shorter survival (median, 3 months) than low group (median, 12 months; P<0.02, generalized Wilcoxon test). Conclusions: These data suggest that serum IL-10 concentration is a possible factor contributing to poor prognosis and low anti-tumor immunity in patients with unresectable hepatocellular carcinoma.

Efficient antigen presentation of soluble, but not particulate, antigen in the absence of Wiskott-Aldrich syndrome protein.

B cells and dendritic cells, lacking functional Wiskott-Aldrich syndrome protein (WASP), have aberrant formation of membrane protrusions. We hypothesized that protrusions may play a role in antigen presentation, and consequently, that impaired antigen presentation may be an underlying factor of the immune deficiency in patients with Wiskott-Aldrich syndrome. In this paper, we investigated the antigen presentation capacity of B cells and dendritic cells from WASP knockout mice, using soluble and particulate antigen, to CD4+ T cells from T-cell receptor transgenic DO11.10 mice. As antigen we used soluble ovalbumin (OVA), a peptide thereof (amino acids 323-339) or bacteria expressing OVA. We found that WASP-deficient B cells and dendritic cells efficiently processed and presented soluble OVA protein as well as its peptide in vitro, inducing proliferation and cytokine production from CD4+ T cells. Antigen presentation of soluble protein was efficient also in vivo, because immunization of WASP-deficient mice with OVA elicited proliferation of transferred, fluorescent-labelled, CD4+ T cells. Although we could detect uptake of bacteria in dendritic cells, processing and presentation of bacterial-expressed OVA was impaired in WASP-deficient dendritic cells. In conclusion, our data suggest that WASP is not needed for processing and presentation of soluble antigen, but that efficient presentation of particulate antigen require WASP.

Impaired expression of CD28 on T cells in hairy cell leukemia.

T cells from patients with active hairy cell leukemia (HCL), a chronic B cell malignancy, show poor proliferation in response to allogeneic peripheral blood mononuclear cells (PBMC). In order to study the T cell dysfunction, the expression of several adhesion and costimulatory molecules was analyzed by flow cytometry. Circulating T cells from HCL patients showed increased percentages of CD28(-) in all T cell subsets. In some patients the percentage of CD28(-) T cells within the CD4(+) subset was increased up to 80%. These CD4(+)CD28(-) T cells did not proliferate in a mixed lymphocyte culture (MLC) against allogeneic PBMC. After enrichment for CD4(+)CD28(+) T cells, the proliferative response in the MLC was recovered, but this response was still lower than the proliferative response from control T cells. In conclusion, lack of CD28 on T cells and a restricted T cell repertoire may contribute to immune deficiency in patients with HCL.

Relationship between progression of disease and immunoglobulin A-anti-Fab-/F(ab ́) 2 autoantibodies in patients with head and neck cancer

Patients with malignant tumors of the head and neck often have immune defects. Higher serum immunoglobulin (Ig)A levels were reported in this group of patients. We investigated whether IgA-anti-Fab- or IgA-anti-F(ab ́) 2 autoantibodies, which have been shown to correlate with severe dysfunction of the immune system, also appear in patients with head and neck cancer. Sera of 110 patients with squamous cell carcinoma (SCCHN), eight patients with adenoid cystic carcinoma, and 57 healthy control subjects were tested by enzyme-linked immunosorbent assay for IgA-anti-Fab autoantibody activity. Patients with head and neck cancer showed a higher IgA-anti-Fab activity (optical density [OD] = 399; n = 118) than did healthy control subjects (OD = 84; n = 57; p < 0.0001). An association between stage of disease and IgA-anti-Fab activity could be established in patients with SCCHN. Patients with stage IV disease had a significantly higher IgA-anti-Fab activity (OD = 538; n = 51) than had patients with stage I disease (OD = 283; n = 18; p < 0.05). Patients with stage II (OD = 293; n = 13) or stage III (OD = 379; n = 28) disease had intermediate activity. Also a higher IgA-anti-Fab activity than in healthy control subjects could be shown in the eight patients with adenoid cystic carcinoma (OD = 314; n = 8; p < 0.01). The highest IgA-anti-Fab activity was observed in eight patients with SCCHN who died within 6 months after testing (OD = 1004; n = 8), suggesting an association between autoimmunity and final disintegration of physiologic body functions. The occurrence of IgA-anti-Fab/IgA-anti-F(ab ́) 2 autoantibodies might be interpreted as an aspect of immune deficiency in patients with malignant tumors of the head and neck. (Otolaryngol Head Neck Surg 1998;118:130-6.)