Biomedical subjects

J Grunewald

Publications and source records attributed to J Grunewald.

At least 19 recordsLinked to original sources

PubMed2006

Coeliac disease and risk of tuberculosis: a population based cohort study.

BACKGROUND: Coeliac disease (CD) is an autoimmune disease often characterised by malnutrition and linked to a number of complications such as an increased risk of lymphoma, adverse pregnancy outcome, and other autoimmune diseases. Tuberculosis (TB) affects a large proportion of the world population and is more common in individuals with malnutrition. We investigated the risk of TB in 14 335 individuals with CD and 69 888 matched reference individuals in a general population based cohort study. METHODS: Cox proportional hazards method was used to calculate the risk of subsequent TB in individuals with CD. In a separate analysis, the risk of CD in individuals with prior TB was calculated using conditional logistic regression. RESULTS: CD was associated with an increased risk of subsequent TB (hazard ratio (HR) 3.74, 95% CI 2.14 to 6.53; p < 0.001). Similar risk estimates were seen when the population was stratified for sex and age at CD diagnosis. Individuals with CD were also at increased risk of TB diagnosed in departments of pulmonary medicine, infectious diseases, paediatrics, or thoracic medicine (HR 4.76, 95% CI 2.23 to 10.16; p < 0.001). The odds ratio for CD in individuals with prior TB was 2.50 (95% CI 1.75 to 3.55; p < 0.001). CONCLUSIONS: CD is associated with TB. This may be due to malabsorption and lack of vitamin D in persons with CD. Individuals with TB and gastrointestinal symptoms should be investigated for CD.

Adolescent↗

PubMed2006

Altered apoptosis in bronchoalveolar lavage lymphocytes after allergen exposure of atopic asthmatic subjects.

The increased number of lymphocytes in airways during an asthmatic response is believed to be the result of increased recruitment of these cells. However, it is possible that a decreased apoptotic rate could also contribute to the increased number. The aim of the present study was to investigate whether allergen airway provocation influences the apoptotic phenotype of lung and peripheral blood lymphocytes (PBL) in subjects with atopic asthma. Bronchoalveolar lavage (BAL) lymphocytes and PBL from 12 asthmatic subjects previously challenged with allergen (n = 7) or saline (n = 5) were exposed to the apoptotic stimulus tributyltin (TBT) in vitro and assayed for apoptosis. Airway allergen provocation resulted in decreased sensitivity of BAL lymphocytes to TBT-induced apoptosis, with 42.2% (range 33.9-62.5%) apoptotic cells before challenge versus 23.5% (range 15.3-42.4%) after challenge, while PBL were unaffected. The increased apoptosis resistance correlated with higher numbers of Bcl-2-expressing lymphocytes. Interestingly, baseline caspase-3-like activity was significantly elevated in viable BAL lymphocytes compared with viable PBL, and was unaltered by allergen exposure. In conclusion, allergen inhalation renders bronchoalveolar lavage lymphocytes more resistant to apoptosis while peripheral blood lymphocytes were not influenced at all, indicating that the apoptotic phenotype of airway lymphocytes may play a role in asthmatic inflammation.

Adult↗

PubMed2006

Changes in immune regulation in response to examination stress in atopic and healthy individuals.

BACKGROUND: Stress can aggravate the allergic inflammation, but determinants of disturbed immune regulation are largely unknown. OBJECTIVE: To determine systemic immunological, local inflammatory and functional airway responses to stress in healthy and atopic individuals. METHODS: Forty-one undergraduate students, 22 with allergy of whom 16 had asthma, and 19 healthy controls, were studied in a low-stress period and in association with a large exam. Subjects completed questionnaires on stress and health behaviours, underwent lung function tests, bronchial methacholine challenge, measurements of exhaled nitric oxide and urine cortisol. Blood cells were phenotyped, and cytokines from mononuclear blood cells were analysed. RESULTS: Perceived stress and anxiety increased in both groups during the exam period while cortisol increased only in the atopy group. Cytokine production decreased broadly in response to stress in both groups, which was paralleled by an increase in the proportion of regulatory T cells (CD4(+)CD45RO(+)CD25(bright)). Interestingly, atopic individuals, but not controls, reacted with a decreased T-helper type 1/T-helper type 2 (Th1/Th2) ratio and a decrease in natural killer (NK) cell numbers in response to stress. In control subjects only, exhaled nitric oxide decreased and forced expiratory volume in one second increased during stress. CONCLUSION: Atopic and non-atopic subjects shared some immune changes in response to stress, such as a dramatic decline in cytokines and an increase in the number of regulatory T cells in peripheral blood. However, other stress-induced immune changes were unique to atopic individuals, such as a skewed Th1/Th2 ratio and reduced NK cell numbers, indicating that some pathogenic mechanisms in atopics may be more strongly affected by stress than others.

Adult↗

PubMed2006

Reduced Th1 response in the lungs of HLA-DRB1*0301 patients with pulmonary sarcoidosis.

To investigate why human leukocyte-associated antigen-DRB1*0301 (HLA-DRB1*0301) positive Scandinavian patients have a better prognosis than HLA-DRB1*0301 negative patients, the present authors examined patterns of cytokine expression in bronchoalveolar lavage (BAL) cells and BAL fluid (BALF) from patients with pulmonary sarcoidosis and controls. Using real-time PCR, the mRNA expression of selected cytokines in BAL cells from newly diagnosed, untreated nonsmoking patients (n=25) and controls (n=11) was quantified. Cytokine protein levels in BALF from patients (n=34) and controls (n=11) were assessed using cytometric bead array. The patients were evaluated and stratified into two subgroups: HLA-DRB1*0301 positive (all with an acute onset) and HLA-DRB1*0301 negative (all with an insidious onset). When comparing patients and controls, BAL cells of the patients expressed significantly higher levels of interferon (IFN)-gamma and interleukin (IL)-10 mRNA. There were significantly decreased IFN-gamma and tumour necrosis factor (TNF)-alpha mRNA levels, and a tendency toward higher levels of transforming growth factor-beta1 mRNA in HLA-DRB1*0301 positive compared with HLA-DRB1*0301 negative patients. Protein levels of IL-1beta, IL-2, IL-6, IL-12p70 and TNF-alpha in BALF were significantly higher in patients. HLA-DRB1*0301 positive patients exhibited tendencies to lower levels of most cytokines in BALF. In conclusion, the present data show a reduced expression of T-helper cell type-1 cytokines in human leukocyte-associated antigen-DRB1*0301 positive patients, which may relate to their good prognosis.

Adult↗

PubMed2005

Phenotypic analysis of alveolar macrophages and lymphocytes following allergen inhalation by atopic subjects with mild asthma.

BACKGROUND: The airway inflammation associated with allergic asthma is initiated through a complex interaction of antigen-presenting cells (APC) and T lymphocytes resulting in the release of a cascade of cytokines regulating the progress of the allergic inflammatory response. In the present study the state of alveolar macrophage (AM) and T cell activation was investigated following induction of allergic airway inflammation in individuals with atopic asthma. METHODS: Eleven individuals with mild, atopic asthma received cumulated allergen inhalations. Before and one day after challenge, bronchoalveolar lavage (BAL) was performed, and peripheral blood samples obtained. Ten healthy individuals served as controls. The expression of cell surface markers by BAL fluid AMs and T cells, and by blood T cells, was investigated by flow cytometry. RESULTS: All patients developed early asthmatic reactions (EAR) with increased numbers of eosinophils and mast cells in BAL fluid following allergen challenge. After allergen challenge, patients had relatively fewer pulmonary CD4+ T cells expressing CD69 and HLA class II and also relatively fewer pulmonary CD8+ T cells expressing HLA class II, compared to before challenge. An increased quantitative expression of CD14 and CD86 was seen within the AM population following allergen challenge. CONCLUSION: The results indicate a recruitment of non-activated, immature macrophages and CD4+ T cells to the airways as well as an altered phenotype pattern within the AM population following induction of allergic airway inflammation by allergen inhalation challenge in asthma.

Adult↗

PubMed2005

Accumulation of eosinophils and T-lymphocytes in the lungs after exposure to pinewood dust.

Exposure to wood dust within the woodworking industry has been shown to cause a variety of respiratory disorders. The aim of this study was to investigate the cellular effects in bronchoalveolar lavage (BAL) fluid and peripheral blood from healthy individuals exposed to pinewood dust. Eleven healthy volunteers were exposed to pinewood dust for 1 h in a whole-body exposure chamber. BAL fluid and blood cells were differentially counted and the expression of activation, adhesion and subset markers on alveolar macrophages and T-lymphocytes was determined 2-6 weeks before and 20 h after the exposure. Following pinewood dust exposure, the total BAL fluid cell concentration increased from 81.4 (64.1-97.5) x 10(6) cells x L(-1) (median (interquartile range)) to 195.3 (154.6-341.2) x 10(6) cells x L(-1). The BAL fluid T-lymphocyte concentration increased from 3.8% (3.5-6.5%) to 7.6% (4.9-11.2%), and BAL fluid eosinophil concentration from 0.0% (0.0-0.2%) to 1.8% (0.6-3.5%). Inhalation of pinewood dust leads to the recruitment of inflammatory cells to the airways of healthy individuals. The increase in numbers of eosinophils, T-lymphocytes and mast cells, i.e. cells of crucial importance to airway inflammation, in the lungs may be related to the increased risk of developing respiratory disorders among woodworkers.

Adult↗

PubMed2005

Characterisation of natural killer cells and CD56+ T-cells in sarcoidosis patients.

The aim of the current study was to investigate the frequency, phenotype and functional activity of natural killer (NK) cells and CD56+ T-cells in the bronchoalveolar lavage fluid and peripheral blood of patients with pulmonary sarcoidosis when compared with healthy volunteers, using staining with a panel of monoclonal antibodies followed by flow cytometry. The results revealed that the majority of the lung NK cell subpopulation expressed CD56(bright). In contrast, there was a predominant CD56(dim) subset in the blood of both patients and healthy controls. Most lung NK cells expressed C-type lectin-like human leukocyte antigen (HLA)-E-specific inhibitory receptor (i.e. CD94/NKG2A), but only a few lung NK cells expressed killer cell immunoglobulin-like inhibitory receptors specific for HLA-A, -B or -C molecules. In addition, a significantly increased number of CD56+ T-cells were observed in the blood of patients when compared with controls. Upon in vitro stimulation, both lung NK and CD56+ T-cells produced considerable amounts of interferon-gamma and tumour necrosis factor-alpha. Thus, in the lungs of patients with pulmonary sarcoidosis, a distinct phenotype of natural killer cells with the capacity to produce cytokines and actively participate in the T-helper 1-like inflammatory response associated with sarcoidosis was identified.

Adult↗

PubMed2004

No serological evidence of Rickettsia helvetica infection in Scandinavian sarcoidosis patients.

Many agents have been suggested to elicit sarcoidosis, and, recently, an association was presented between this disease and the bacterium Rickettsia helvetica. The aim of this study was to investigate if serological support for such an association could be detected. Sera from 20 well-characterised sarcoidosis patients were investigated for anti-rickettsial immunoglobulin G antibodies with a micro-immunofluorescence technique. R. helvetica, R. conorii and R. typhi served as antigens. In conclusion, none of the investigated sera displayed detectable titres of anti-rickettsial immunoglobulin G antibodies. Thus, the current study does not support an association between rickettsia and sarcoidosis.

Adult↗

PubMed2004

T cell receptor V gene usage by CD4+ and CD8+ peripheral blood T lymphocytes in immune thrombocytopenic purpura.

AIM: To identify T cell expansions, i.e. increased frequencies of T cells using a particular T cell receptor (TCR) V alpha or V beta gene segment, in patients with immune thrombocytopenic purpura (ITP). METHODS: The TCR repertoires of CD4+ and CD8+ peripheral blood lymphocytes of 16 patients with chronic ITP were analysed by staining with a panel of anti-TCR V alpha and V beta antibodies followed by flow cytometry. RESULTS: Four of the 16 patients exhibited a total of 6 expansions of CD8+ T cells using a particular V beta segment, but no expansions were detected in the CD4+ subset. For three of the expansions where a follow-up blood sample after treatment with intravenous immunoglobulin was available, only one expansion remained. CONCLUSION: Overall T cell expansion frequency was the same as in healthy individuals. However, the presence of expansions that normalized with treatment suggests the presence of specific T cells implicated in the pathogenesis of ITP.

Adolescent↗

PubMed2003

T-cell activation and the development of an apoptosis-resistant CD45RO+ T-cell population.

Growing experimental evidence supports a broadening role for the caspases; not only do they participate in the process of apoptosis but also in the control of the cell cycle and cellular proliferation. The biological role of the caspases in the process of T-cell activation and proliferation is still not defined. In the present study, we propose a potential role, by demonstrating an association of T-cell receptor-mediated caspase activity with the development of an apoptosis-resistant memory CD45RO+ T-cell population. As previously shown by us, a time-dependent induction of caspase activity, in the absence of apoptosis, can be observed in CD3-stimulated human peripheral blood lymphocytes. We here show that a population of CD45RO+ cells, with activated caspase-3 and with resistance to tributyltin-induced apoptosis, develops after 3 days of stimulation. A concomitant expression of the anti-apoptotic protein Bcl-xL accompanied the caspase activity and the development of the apoptosis-resistant phenotype. Finally, upon co-culturing with dexamethasone (DEX), the CD3-induced caspase-3 activity was blocked. During this condition, the expression of the activation marker HLA-DR as well as the cellular proliferative response was strongly suppressed. The development of memory cells with a CD45RO+ phenotype was also blocked. Our data support the hypothesis that caspase-3 activity, observed in CD3-stimulated cells, may be an important component in the proliferation process and, furthermore, might play a role for the development of memory T cells, and DEX inhibits this process.

Apoptosis↗

PubMed2003

Expression of Th1 markers by lung accumulated T cells in pulmonary sarcoidosis.

OBJECTIVES: The balance between Th1 and Th2 T cells, classified by virtue of their cytokine production can in an immune response influence the phenotype and progression of several clinical diseases. In this study, we examined the expression of Th1 associated chemokine and cytokine receptors CXCR3, CCR5, and interleukin (IL)-12R, IL-18R, respectively, as well as of the Th2 associated chemokine receptors CCR4 and CXCR4 on CD4+ and CD8+ T cells. SUBJECTS: Eighteen patients with untreated pulmonary sarcoidosis. MATERIALS AND METHODS: We used monoclonal antibodies and flow cytometry to analyse the expression of chemokine receptors CXCR3, CXCR4, CCR4 CCR5 and cytokine receptors IL-12R, IL-18R in combination with anti-CD4 and anti-CD8 mAbs in bronchoalveolar lavage fluid (BAL) and peripheral blood lymphocytes (PBL) from sarcoidosis patients. RESULTS: There were significantly more BAL CD4+ T cells expressing CXCR3, CCR5, IL-12R and IL-18R compared with paired PBL CD4+ T cells. In contrast, the Th2 associated chemokine receptors CXCR4 and CCR4 were expressed by a fewer percentage of BAL CD4+ compared with PBL CD4+ T cells. There was a positive correlation between the percentage of BAL lymphocytes and the number of CXCR3 and CCR5 expressing CD4+ BAL T cells. Also, the number of CD4+ IL-18R+ BAL fluid cells correlated negatively with disease duration. CONCLUSIONS: The lung accumulation of CXCR3, CCR5, IL-12R and IL-18R expressing T cells is in line with previous reports showing elevated levels in the lung of the corresponding ligands in sarcodosis. Blocking such ligands and/or receptors may develop into a future immunomodulatory therapy.

Adult↗

PubMed2003

Lung accumulations of eosinophil granulocytes after exposure to cornstarch glove powder.

Starch is a main component of wheat flour, which, besides being an occupational allergen can also induce irritative symptoms in the airways. A purified starch product (cornstarch glove powder) was used to investigate whether starch alone could induce airway inflammation. The aim of the study was to investigate a role for starch in wheat flour-induced airway inflammation. Ten healthy individuals were exposed to cornstarch glove powder in a whole-body exposure chamber. Bronchoscopy with bronchoalveolar lavage (BAL) was performed 2-3 weeks before and 1 day after exposure, and the BAL cells were counted differentially. In addition, the expression of activation, adhesion and subset markers on alveolar macrophages and BAL T-cells were investigated using flow cytometry. A three-fold increase in BAL cell concentrations was found, with a selective accumulation and activation of eosinophilic granulocytes, as well as an influx of nonactivated monocytes and polyclonal CD4+ T-cells into the airways. The results show that inhalation of cornstarch glove powder leads to the development of a subclinical inflammation in the airways, with an accumulation of eosinophilic granulocytes. The authors suggest that such exposure may be an interesting model for studying factors contributing to lung accumulations of eosinophil granulocytes in humans.

Administration, Inhalation↗

PubMed2003

Exosomes with major histocompatibility complex class II and co-stimulatory molecules are present in human BAL fluid.

Exosomes are 30-100 nm diameter vesicles formed by inward budding of endosomal compartments and are produced by several cell types, including T-cells, B-cells and dendritic cells (DC)s. Exosomes from DCs express major histocompatibility complexes (MHC) class I and II, and co-stimulatory molecules on their surface, and can induce antigen-specific activation of T-cells. The aims of the present study were to investigate for the presence of exosomes in bronchoalveolar lavage fluid (BALF) from healthy individuals, and to establish if these exosomes bear MHC and co-stimulatory molecules. The authors analysed BALF taken from seven healthy volunteers and used exosomes from monocyte-derived DC (MDDC) cultures as a reference. After ultracentrifugation, exosomes were bound to anti-MHC class II coated magnetic beads and analysed by flow cytometry and electron microscopy. The authors report for the first time that exosomes are present in BALF. These exosomes are similar to MDDC derived exosomes as they express MHC class I and II, CD54, CD63 and the co-stimulatory molecule CD86. The results demonstrate that exosomes are present in the lung, and since they contain both major histocompatibility complex and co-stimulatory molecules it is likely that they are derived from antigen presenting cells and might have a regulatory role in local immune defence.

Adult↗

PubMed2003

Markers of activity in clinically recovered human leukocyte antigen-DR17-positive sarcoidosis patients.

Scandinavian human leukocyte antigen-DR17-positive (DR17+) sarcoidosis patients are characterised by a good prognosis. They also reveal an accumulation in bronchoalveolar lavage fluid of T-lymphocytes expressing the T-cell receptor V gene segment AV2S3 at disease onset. The authors of this study wished to establish whether AV2S3 T-lymphocyte accumulation changes from disease onset to clinically resolved disease and how this relates to other activity parameters. Bronchoalveolar lavage fluid and serum from nine DR17+ sarcoidosis patients were examined at disease onset and after spontaneous resolution of clinical and radiographical signs of disease. Nine DR17+ patients with lung accumulated CD4+ AV2S3+ T-cells were investigated after clinically recovery. At re-examination the percentage of CD4+ AV2S3+ lymphocytes in bronchoalveolar lavage fluid was normalised (29 versus 5.4%). A significant reduction in lymphocyte percentage (14 versus 4.4%) and a decrease in cellular concentration (179x10(6) x L(-1) versus 111x10(6) x L(-1)) and CD4/CD8 ratio (5.2 versus 2.4) were also seen. In serum, the activity of angiotensin-converting enzyme (24.9 versus 14.0 U x mL(-1)) as well as the levels of neopterin (7.8 versus 5.3 nmol x L(-1)) decreased significantly after recovery. These results indicate that the locally accumulated AV2S3 positive T-lymphocytes in bronchoalveolar lavage are involved in the pathogenic process of sarcoidosis in this patient group.

Adult↗

PubMed2003

Changes in bronchoalveolar lavage fluid proteins in sarcoidosis: a proteomics approach.

In sarcoidosis, an inflammatory lung disease, the protein profile of bronchoalveolar lavage fluid (BALF) is altered. To study the BALF protein pattern changes in sarcoidosis, samples from six patients and four healthy individuals were analysed by two-dimensional polyacrylamide gel electrophoresis. A comparison of the protein-spot patterns showed a significantly higher number of protein spots in the pH range 5.5-6.7 in patients compared to controls (472 versus 384). Furthermore, the number of protein spots in the patients were significantly decreased in the acidic pH range 4.5-5.5 (399 versus 518). Measurement of the optical density in the gels showed varying expression levels for several protein spots. Seventeen of the altered protein spots were identified, of which seven have previously not been reported for BALF. Many of these are nonplasma proteins involved in the inflammatory and oxidant-antioxidant processes. In conclusion, the bronchoalveolar lavage fluid protein content is altered in sarcoidosis patients, especially for proteins that are not derived from plasma. The described proteomics approach will in the future be used to asses overall changes in the protein content associated with sarcoidosis and may offer the possibility of identifying disease-specific proteins.

Adult↗

PubMed2002

Angiotensin-converting enzyme gene polymorphism in relation to HLA-DR in sarcoidosis.

OBJECTIVES: To investigate if an insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene associates with HLA-DR alleles previously found to be of prognostic interest in Scandinavian sarcoidosis patients. This may contribute to characteristics associated with these HLA-DR alleles, such as a good (DR17) or poor (DR14 or 15) prognosis. DESIGN, SETTINGS AND SUBJECTS: Polymerase chain reaction (PCR) was used for analysing an I/D polymorphism in the gene coding for ACE in 138 subjects; 65 controls and 73 sarcoidosis patients, and for HLA-DR genotyping 67 patients. Serum ACE level (S-ACE) was measured in all controls and 72 patients. Sixty-one patients were classified as chronic or nonchronic after 2 years follow-up. All patients were recruited and followed at our outpatient clinic. RESULTS: No significant differences in ACE alleles or genotypes were seen between controls and patients or between patients positive and negative for DR17 or DR14/15. The ACE genotype did not differ between nonchronic and chronic patients. The ACE genotype tended to influence the S-ACE in patients, whilst in controls S-ACE significantly differed between the ACE genotypes. CONCLUSION: This study does not support an association between ACE genotype and sarcoidosis or disease outcome. However, because significantly (P < 0.001) more DR17 positive (17 of 19) than DR14/15 positive (seven of 26) patients were classified as nonchronic, these results instead strengthen the prognostic importance of HLA-DR alleles in Scandinavian sarcoidosis patients.

Adult↗

PubMed2002

Apoptosis resistant bronchoalveolar lavage (BAL) fluid lymphocytes in sarcoidosis.

BACKGROUND: Sarcoidosis is a chronic granulomatous lung disease of unknown origin. The accumulation of activated T cells at sites of inflammation represents an early stage in granuloma formation. Since mechanisms governing the normal resolution of inflammatory processes are poorly understood, this study aimed to investigate the apoptotic phenotype of peripheral blood and lung T lymphocytes from patients with sarcoidosis. METHODS: Bronchoalveolar lavage (BAL) was performed in 10 patients with active sarcoidosis and five healthy controls. RESULTS: Virtually no lymphocyte apoptosis, as determined by annexin V or Hoechst staining, was seen in either patients or controls. Sustained caspase-3 activity in non-apoptotic BAL fluid lymphocytes of the patients was detected, however, in agreement with in vitro studies demonstrating caspase activation after T cell receptor (TCR) triggering as a physiological response required for efficient T cell activation. Only 11.0% (range 7.7-17.6) of the BAL lymphocytes from sarcoidosis patients were annexin V positive after exposure to the apoptotic stimulus tributyltin compared with 55.0% (range 42.0-62.0) of BAL lymphocytes from healthy controls (p<0.001). After anti-Fas treatment only 8.5% (range 6-10) of BAL fluid lymphocytes from patients but 45.5% (range 38-62) from healthy controls were apoptotic. CONCLUSION: BAL fluid lymphocytes from patients with sarcoidosis display a non-apoptotic morphology associated with endogenous caspase-3 activity. They seem to be resistant to apoptosis, which might contribute to the accumulation of inflammatory cells in the lungs, persistence of inflammation, and the development and maintenance of granuloma.

Adult↗

PubMed2002

Lung restricted T cell receptor AV2S3+ CD4+ T cell expansions in sarcoidosis patients with a shared HLA-DRbeta chain conformation.

BACKGROUND: Sarcoidosis is a systemic disease of unknown aetiology frequently affecting the lungs. CD4+ T cells, in particular, accumulate in the lungs, implicating them in the pathogenesis of the disease. METHODS: T cell receptor (TCR) variable (V) gene expression on bronchoalveolar lavage (BAL) fluid T cells and the HLA DR alleles of 121 Scandinavian patients with sarcoidosis was determined. RESULTS: As expected from our previous results, almost every DRB1*0301 (i.e. DR17) positive patient (67/69) had significantly increased numbers of AV2S3+ CD4+ T cells in the BAL fluid but normal levels in peripheral blood (that is, lung restricted expansions) compared with only six of 52 DRB1*0301 negative patients. Detailed genotypic HLA analysis showed that these six DRB1*0301 negative patients with lung restricted AV2S3+ T cell expansions had another HLA allele in common-the HLA-DRB3*0101 allele (also called DR52a)-which was not found in any other DRB1*0301 negative patient. A new group of sarcoidosis patients was therefore identified, characterised by a strict correlation between a distinct HLA allele and lung accumulated T cells expressing a particular TCR V segment. Furthermore, the HLA-DRB1*0301 and HLA-DRB3*0101 encoded molecules showed similarities, with identical amino acid sequences in regions important for antigen binding which may enable them to bind and present the same or similar antigenic peptides. CONCLUSIONS: HLA-DRB3*0101 as well as DRB1*0301 positive sarcoidosis patients may have the capacity to present specific sarcoidosis associated antigens in such a way that AV2S3+ CD4+ T cells are stimulated preferentially, generating lung restricted AV2S3+ T cell expansions.

Adult↗