Molecules of Damage-Associated Patterns in Bronchoalveolar Lavage Fluid and Serum in Chronic Obstructive Pulmonary Disease.

Chronic exposure to detrimental environmental factors may induce immunogenic cell death of structural airway cells in chronic obstructive pulmonary disease (COPD). Damage-associated molecular patterns (DAMPs) is a family of heterogeneous molecules released from injured or dead cells, which activate innate and adaptive immune responses on binding to the pattern recognition receptors on cells. This study seeks to define the content of DAMPs in the bronchoalveolar lavage fluid (BALF) and serum of COPD patients, and the possible association of these molecules with clinical disease features. Thirty COPD in advanced disease stages were enrolled into the study. Pulmonary function tests, arterial blood gas content, 6-minute walk test, and BODE index were assessed. The content of DAMPs was estimated using the commercial sandwich-ELISA kits. We found differential alterations in the content of various DAMP molecules. In the main, BALF DAMPs positively associated with age, forced expiratory volume in one second (FEV1), and residual volume (RV); and inversely with PaO2, residual volume/total lung capacity (RV/TLC) ratio, and the disease severity staging. In serum, DAMPS positively associated with the intensity of smoking and inversely with age, PaO2, and TLC. In conclusion, DAMPs are present in both BALF and serum of COPD patients, which points to enhanced both local in the lung environment as well as systemic pro-inflammatory vein in this disease. These molecules appear involved with the lung damage and clinical variables featuring COPD. However, since the involvement of various DAMPs in COPD is variable, the exact role they play is by far unsettled and is open to further exploration.

A case of bizarre posttransplant anti-glomerular basement membrane disease.

The non-collagenous (NC1) domain of α3 and α5 chains of type IV collagen are eminent targets of abnormal immune response in anti-glomerular basement membrane (anti-GBM) disease, which can be diagnosed by the presence of strong linear IgG staining along GBM detected by direct immunofluorescence. The presence of linear GBM fixation in renal allograft is a rare finding. We observed a 33-year-old male with de novo renal failure in a kidney transplant. An examination of a kidney biopsy specimen revealed, in light microscopy, mild mesangial hypercellularity together with mild focal interstitial fibrosis and sparse inflammatory infiltrate. In immunofluorescence microscopy strong linear IgG staining along the capillary walls was seen. Serum anti-GBM antibodies were negative and no mutation in exons coding NC1 domains of α3 and α5 chains of type IV collagen were detected. We described a rare case of a patient with atypical anti-GBM disease in renal allograft, caused probably by the same process which affected the native kidneys.

Pleural Macrophages can Promote or Inhibit Apoptosis of Malignant Cells via Humoral Mediators Depending on Intracellular Signaling Pathways.

Macrophages in malignant pleural effusions (MPEs) demonstrate a promalignant phenotype. They release mediators, which are a source of inflammation within the pleura. We established in vitro model proving that pleural macrophages isolated from effusions affect cancer cells in their pro- or anti-apoptotic activity via humoral mediators. Additionally, we measured concentrations of selected transcription factors in cancer cells. Pleural macrophages can affect the apoptosis of cancer cells via intercellular mediators which trigger different signal transductors in cancer cells. The observed effect is connected to the composition of exudate which may vary depending on its origin, either malignant or nonmalignant.

Higher expression of inhibitory CD158b and CD158e NK cell receptor and age predicts treatment response in children with chronic hepatitis C.

Treatment with pegylated interferon-α and ribavirin (PEG-IFN/RBV) is the only choice for chronic hepatitis C (CHC) in children. Natural killer (NK) cells were described to play a vital role in CHC. The aim of this study was to analyze the expression of peripheral blood NK cell receptors in their relation to PEG-IFN/RBV treatment response. Study included 26 children with CHC-13 boys, age range 13.42 ± 3.28 years. Blood for biochemical, virological and cytometric testing was taken for evaluation prior to the antiviral treatment. NK cell receptors were detected by flow cytometry and the results were presented as proportion of cells and mean fluorescence intensity (MFI). Therapy consisted of PEG-IFNα-2b (60 µg/m2 s.c 1×/week) and RBV (15 mg/kg p.o. daily). Treatment duration was response-related and varied from 12 to 72 weeks. Rapid virological response (RVR) was evaluated in the 4th week and sustained virological response (SVR) 6 months after completion of the therapy. RVR children were younger (11.67 ± 3.74 vs 15.35 ± 2.42; p = 0.001) and displayed higher CD158b (3.58 ± 0.16 vs 3.45 ± 0.13; p = 0.038) and CD158e expression (4.33 ± 0.21 vs 4.03 ± 0.16; p = 0.039). Density of CD158b (logMFI = 3.68 ± 0.22 vs 3.36 ± 0.16; p = 0.036) and CD158e expression was significantly higher (4.37 ± 0.14 vs 4.12 ± 0.21; p = 0.046) and NKG2D expression significantly lower (97.50 ± 3.46 vs 94.92 ± 5.93; p = 0.049) in SVR children. SVR children were also significantly younger (12.40 ± 3.66 vs 15.13 ± 2.83; p = 0.003). Significance of the age of patients, and expression of CD158b and CD158e were confirmed in univariate and multivariate analysis. Age of patients is negatively related to RVR and SVR. NK cell phenotype with higher expression density of CD158b and CD158e receptor was a positive predictor of SVR.

Comparative Seroprevalence of Hepatitis A And E Viruses in Blood Donors from Wielkopolska Region, West-Central Poland.

The objective of the present study was to investigate the seroprevalence of HAV and HEV in Polish blood donors (BDs). One hundred and ten randomly selected healthy BDs, living in Wielkopolska Region were tested for anti-HAV IgG and anti-HEV IgG with commercial assays. The seroprevalence of anti-HAV was 11.8%; anti-HEV were detected in 60.9% of BDs (p < 0.0001). Consumption of risky food was more common in anti-HEV-positive BDs (59.1% vs. 33.3%; p = 0.01). Twelve out of 20 BDs (60%) with no history of travel abroad were exposed to HEV. Wielkopolska Region, Poland should be regarded as a new HEV infection-hyperendemic area in Europe.

Expression of Natural Killer Cell Inhibitory Receptors is Associated with Significant Liver Injury in Chronic Hepatitis C in Children.

INTRODUCTION AND AIM: Natural Killer (NK) cells play an important role in innate immune response to viral infections and their high proportion is situated in the liver. The aim of this study was to analyze possible relation between the expression of NK cell receptors and varied intensity of liver lesions in chronic hepatitis C (CHC) in children. MATERIAL AND METHODS: Study included 105 children with CHC - 54 boys and 51 girls, age 13.62 ± 3.48 years. Blood specimens were taken at the day of the liver biopsy. Histological evaluation was performed according to METAVIR scoring system. Circulating NK cells were evaluated by flow cytometry. The results were shown as a proportion of cells expressing evaluated receptor and its' mean fluorescent intensity (MFI). RESULTS: In 58 children with CHC (55.2%) significant liver fibrosis was observed ( ≥F2). Higher proportion of cells expressing CD158e inhibitory receptors was observed in the group of children with ALT > 2UNL (21.11 ± 14.60 vs. 12.22 ± 8.99%; p = 0.037). While higher proportion of cells expressing inhibitory CD158b receptor was observed in children with significant fibrosis (F ≥ 2) compared to minimal fibrosis (F < 2) - (34.14 ± 12.44 vs. 27.48 ± 8.71%; p = 0.049). Children with advanced fibrosis (F ≥ 3) had higher MFI of NK cell CD 158b receptor than children with fibrosis scored F < 3 - (5344.20 ± 3407.49 vs. 2979.67 ± 1190.64; p = 0.049). Proportion of NK cells expressing CD158b was found a predictor of significant fibrosis in univariate analysis - [OR 1.065; 95%CI (1.07-1.15); p = 0.046]. CONCLUSIONS: Higher proportion of NK cells expressing inhibitory CD158b and CD158e receptors is associated with significant liver injury.

Pluripotency transcription factors in lung cancer-a review.

Lung cancer is the leading cause of cancer-related mortality worldwide. Diagnosis of lung cancer in an early stage is still a challenge due to the asymptomatic course of early stages of the disease and the lack of a standard screening program for the population. Nowadays, learning about the mechanisms that lead to cancerogenesis in the lung is crucial for the development of new diagnostic and therapeutic strategies. Recently, many studies have proved that cancer stem cells (CSCs) are responsible for the initiation, progression, metastasis, recurrence, and even resistance of chemo- and radiotherapeutic treatment in patients with lung cancer. The expression of pluripotency transcription factors is responsible for stemness properties. In this review, we summarize the current knowledge on the role of CSCs and pluripotency transcription factors in lung carcinogenesis.

Patterns of glomerular disease based on 4-year kidney biopsy material analyzed by light microscopy and immunofluorescence: a retrospective single-center analysis in Poland.

The aim of this study was to assess the epidemiology of different patterns of chronic glomerular diseases based on clinical, histopathological and immunofluorescent findings of glomerulonephritis patients hospitalized in the Department of Nephrology, Transplantology and Internal Diseases in Poznan between January 2009 and December 2012. We retrospectively studied 418 patients who had been subjected to renal biopsies. Data on serum creatinine concentration, 24 h proteinuria, arterial hypertension, diabetes mellitus, and histological and immunofluorescent findings were collected. The patients' mean age was 42 ±15. The male sex prevailed (53.1%). Immunoglobulin A nephropathy was the most common finding (18.9%), followed by focal segmental glomerulosclerosis (16.3%), membranous glomerulonephritis (10.1%), lupus nephritis (8.4%), extracapillary glomerulonephritis (3.3%) and membranoproliferative glomerulonephritis (2.6%). In 69 (16.5%) patients the biopsy was non-informative or non-diagnostic. Patients with membranous nephropathy presented the highest frequency of nephrotic syndrome (71.4%), followed by membranoproliferative glomerulonephritis and focal segmental glomerulosclerosis. Combined analysis of the clinical, histopathological and immunofluorescent findings in glomerulonephritis patients based on a single center's data can provide important epidemiological findings.

Quantitative analysis of elastase and cathepsin G mRNA levels in peripheral blood CD14(+) cells from patients with rheumatoid arthritis.

In rheumatoid arthritis (RA) activity of serine proteases is an important factor contributing to destructive changes in the joints. The aim of this study was to compare elastase (ELANE) and cathepsin G (CTSG) mRNA levels in peripheral blood CD14(+) cells obtained from RA patients, healthy subjects (HS) and patients with osteoarthritis (OA). CD14(+) cells were isolated from peripheral blood by positive magnetic selection. The expression levels of ELANE and CTSG were determined by quantitative real-time PCR. ELANE mRNA expression was significantly higher in RA patients when compared to HS (p<0.001) and OA patients (p<0.001). The results suggest that in RA, peripheral blood CD14(+) cells express serine protease mRNA as a result of systemic mechanisms probably related to inflammation/cytokines before entering inflamed joints.

Effect of HPV Vaccination on Virus Disappearance in Cervical Samples of a Cohort of HPV-Positive Polish Patients.

The introduction of human papillomavirus vaccines revolutionized cervical cancer prevention. Our research hypothesis is that HPV vaccination affects the remission of HPV in cervical swabs. We provide a prospective, ongoing, 24-month, non-randomized study in HPV-positive women. We enrolled 60 patients with positive HPV swabs from the cervix (fifty-one vaccinated with the nine-valent vaccine against HPV and nine unvaccinated). Using an enzyme-linked immunosorbent assay, we determined IgG class antibodies of HPV in the patients' serums. Persistent HPV infection after vaccination was significantly less frequent in the nine-valent vaccinated group (23.5%) compared to the control group (88.9%; p < 0.001). Antibody level after vaccination was significantly higher in the vaccinated patients compared to the control group. The reactive antibody level was seen in the case of all patients in the vaccinated group and one-third of the unvaccinated group (33.3%, n = 3). The vaccination of HPV-positive patients may increase the chance of HPV remission in cervical swabs and may be a worthwhile element of secondary prevention in HPV-positive patients.

Macrophages in malignant pleural effusions - alternatively activated tumor associated macrophages.

Pleural macrophages are involved in local defense mechanisms against environmental pollution, bacteria and cancer. Their main function encompasses phagocytosis of degenerated mesothelial cells. In human pleural effusions macrophages represent more than half of all cells. A model of polarized macrophage activation (M1 and M2) was proposed, which defines a functionally different macrophage populations generated in response to various factors present in the inflamed environment. Tumor associated macrophages are a major component of the inflammatory infiltrate of most cancers. They can promote the proliferation and spread of cancer cells in the early stages of carcinogenesis and during metastasis. Macrophages isolated from malignant pleural effusions as well as tumor associated macrophages exhibit weak cytotoxic activity against tumor cells, increase their proliferative activity and may protect tumor cells from apoptosis. Defining biology of macrophages present in specific environment of the pleural effusion could allow the introduction of innovative diagnostic and therapeutic strategies.

Immunity after HPV Vaccination in Patients after Sexual Initiation.

Vaccinations against human papillomavirus (HPV) are included in the primary prevention of precancerous intraepithelial lesions and HPV-related cancers. Despite the undeniable effectiveness of vaccination in the juvenile population, there is still little research on the effect in patients after sexual initiation. Our study aims to assess anti-HPV (L1 HPV) antibodies in healthy patients and diagnosed cervical pathology after 9-valent vaccination. We provide a prospective, ongoing 12-month, non-randomised pilot study in which 89 subjects were enrolled. We used an enzyme-linked immunosorbent assay to determine IgG class antibodies to HPV. We noted significantly higher levels of antibodies in vaccinated individuals than in the unvaccinated control group. The above work shows that vaccination against HPV might be beneficial in patients after sexual initiation as well as in those already diagnosed with HPV or SIL infection.

Regulatory T cells, damage-associated molecular patterns, and myeloid-derived suppressor cells in bronchoalveolar lavage fluid interlinked with chronic obstructive pulmonary disease severity: An observational study.

ABSTRACT: The role of regulatory T cells (Tregs), damage-associated molecular patterns (DAMPs), and myeloid-derived suppressor cells (MDSCs) in the mechanism of innate and adaptive immune responses in chronic obstructive pulmonary disease (COPD) is not well understood.Evaluating the presence of Tregs in the bronchoalveolar lavage fluid (BALF) and peripheral blood in patients with COPD, and assessment of the relationship between Tregs, MDSCs, and DAMPs as factors activating innate and adaptive immune responses. Description of the association between immune and clinical parameters in COPD.Thirty-one patients with COPD were enrolled. Clinical parameters (forced expiratory volume in one second [FEV1], forced vital capacity, total lung capacity [TLC], diffusion capacity of carbon monoxide, and B-BMI, O-obstruction, D-dyspnea, E-exercise [BODE]) were assessed. Tregs and MDSCs were investigated in the BALF and blood using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry. The levels of defensin (DEF2), galectin-1 (Gal-1), galectin-3 (Gal-3), galectin-9 (Gal-9), heat shock protein-27 (HSP27), and surfactant protein A were assessed via sandwich enzyme-linked immunosorbent assay.The percentage of Tregs was significantly higher in the blood than in the BALF, in contrast to the mean fluorescence intensity of forkhead box P3 (FoxP3). Significant associations were observed between Tregs and HSP27 (r = 0.39), Gal-1 (r = 0.55), Gal-9 (r = -0.46), and MDSCs (r = -0.50), and between FoxP3 and Gal-1 (r = -0.42), Gal-3 (r = -0.39), and MDSCs (r = -0.43). Tregs and clinical parameters, including FEV1%pred (r = 0.39), residual volume (RV)%pred (r = -0.56), TLC%pred (r = -0.55), RV/TLC (r = -0.50), arterial oxygen saturation (r = -0.38), and arterial oxygen pressure (r = -0.39) were significantly correlated. FoxP3 was significantly interlinked with RV/TLC (r = -0.52), arterial oxygen pressure (r = 0.42), and BODE index (r = -0.57).The interaction between innate and adaptive immune responses in patients with COPD was confirmed. The expression of Tregs in BALF may have prognostic value in patients with COPD. The conversion of immune responses to clinical parameters appears to be associated with disease severity.

Evaluation of the phenotype pattern of macrophages isolated from malignant and non-malignant pleural effusions.

Macrophages are among the infiltrate components of most malignant tumors. Tumor-associated macrophages (TAMs) may secrete a variety of humoral factors, which promote or inhibit tumor growth. In general, depending on their activation pathway, macrophages exhibit two different patterns of phenotype, M1 or M2. It is assumed that TAMs comprise pattern M2. In the malignant pleural effusion, macrophages are a frequent component of cytological evaluation. In this microenvironment, TAMs could be involved in the development of immunity. The phenotype of macrophages represented in malignant and non-malignant pleural effusions is unknown. In this study, macrophages were isolated from 38 pleural effusions (15 malignant and 23 non-malignant) and the expression of a variety of immune mediators and their receptors was assessed to determine the type of activation (M1 vs. M2). The expression of mRNA was analyzed for IL-1ß, IL-4, IL-6, IL-10, IL-11, IL-18, TNFα, TGFß1, IL1R1, IL1RAP, TLR2, TLR4, VLA4, CD62L, MMP2, MMP9, VEGFA, PDGFA, and PDGFB. In immunohistochemical evaluation, the expressions of CD68, mesothelin, MAC387, IL-1ß, IL-6, IL-10, IL-12, TNFα, and CD105 were assessed. The cytoplasmic expression of IFNγ, TNFα, IL-6, and IL-10 and the surface expression of CD11a, CD14, CD15, CD16, CD23, CD25, CD45, CD54, CD62L, CD69, VLA2, VLA3, VLA4, VLA6, TLR2, TLR4, and CCR7 were tested using flow cytometry. In supernatants from macrophages cultures, TNFα, IL-1ß, IL-6, IL-8, IL-10, IL-12, MCP1, and VEGF were investigated by cytometric beads array method (CBA flex sets) and TGFß1 by ELISA. Our results indicate that macrophages from malignant and non-malignant pleural effusions differ from each other and suggest that macrophages isolated from non-malignant effusions show a pattern comparable to M1 while those isolated from malignant effusions express similarity to M2 phenotype, but they have not shown a classical M2 pattern.

Genotyping of human papillomavirus DNA in Wielkopolska region.

OBJECTIVES: Human papillomavirus infection is one of the most common sexually transmitted diseases. Long-term exposure to the HPV leads to development of high-grade squamous intraepithelial lesions that can eventually transform into cervical cancer. The aim of the study was to assess the HPV genotype distribution in patients with abnormal pap smear and provide prospective study. MATERIAL AND METHODS: We obtained material from 674 women who registered to Specialist Medical Practice in the years 2008-2020. The sample for the molecular test was collected using combi brush and forwarded to the independent, standardized laboratory. HPV detection was done using PCR followed by DNA enzyme immunoassay and reverse hybridization line probe assay for virus genotyping. Sequence analysis was performed to characterize virus genotypes in HPV - positive samples. RESULTS: We found that 53% of patients tested positive for HPV. The percentage decreased with age. The following HPV types were the most common: HPV - 16 (24.5%), HPV - 53 (13.1%), HPV - 31 (10.3%), HPV - 51 (9.7%), HPV - 56 (9.5%). To our knowledge, this study is the largest assessment of HPV genotypes in Poland. CONCLUSIONS: Our results suggest that type-specific, high-risk HPV DNA - based screening should focus on HPV types 16, 31, 51, 56.

Billet Straightening by Three-Point Bending and Its Automation.

This paper presents the current results of cooperation focused on automatic billet straightening machine development. First, an experimental study of three-point bending realized on small specimens is presented to explain the basic ideas of the straightening. Then, the main regimes of straightening and the algorithm itself are described together. Subsequent finite element simulations of operational experiments show the applicability of the developed theory. The significance of material parameters estimation is depicted in this work. At least four parameters have to be properly determined for a new material in the straightening process.

Damage-Associated Molecular Patterns and Myeloid-Derived Suppressor Cells in Bronchoalveolar Lavage Fluid in Chronic Obstructive Pulmonary Disease Patients.

Myeloid-derived suppressor cells (MDSCs) are present in the human lung microenvironment, and they may be involved in the local inflammatory process in chronic obstructive pulmonary disease (COPD). Chronic inflammation in COPD may induce immunogenic cell death of structural airway cells, causing the release of damage-associated molecular patterns (DAMPs). DAMPs may activate the innate and adaptive immune system. The relationship between MDSCs and DAMPs in COPD is poorly described in the available literature. Objectives. (1) Assessment of MDSC percentage and DAMP concentration in bronchoalveolar lavage fluid (BALF) and peripheral blood. (2) Analysis of the relationship between MDSC percentage and chosen DAMPs. Patients and Methods. 30 COPD patients were included. Using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry, MDSCs were assessed in BALF and peripheral blood. The concentration of DAMPs was estimated using sandwich ELISA. Using the Bradford method, the total protein concentrations were evaluated. Results. The percentage of MDSCs among MC in BALF correlated well with the concentration of defensin and heat shock protein 27. Assessing the percentage of MDSCs among all leukocytes in BALF, we revealed a significant correlation with the concentration of defensin, hyaluronic acid, and surfactant protein A. No dependencies occurred between DAMPs and MDSCs in peripheral blood. Conclusion. MDSCs and DAMPs occur in the COPD patient lung microenvironment. Significant correlations between them found in BALF may indicate their influence on the local inflammatory process in COPD. These relationships allow better understanding of the inflammatory process in COPD.

The effect of caveolin-1 knockdown on interleukin-1ß-induced chemokine (C-C motif) ligand 2 expression in synovial fluid-derived fibroblast-like synoviocytes from patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease leading to destructive changes in peripheral joints and their irreversible deformity. The influx of chemoattractant-mediated inflammatory cells to the joints is one of the main features of RA. OBJECTIVES: The aim of this study was to investigate the effect of a knockdown of caveolin-1 (CAV1), a known regulator of multiple cell signaling pathways, on chemokine (C-C motif) ligand 2/monocyte chemoattractant protein-1 (CCL2/MCP-1) expression in synovial fluid-derived fibroblast-like synoviocytes (sfd-FLSs) obtained from patients with RA. MATERIAL AND METHODS: Primary cell cultures of sfd-FLSs were established from RA synovial fluids. Cells were transiently transfected with small interfering RNA (siRNA) specific for CAV1, and then incubated with interleukin (IL)-1ß to induce CCL2 expression. The expression levels of CAV1 and CCL2 were assessed at transcript level, using quantitative polymerase chain reaction (qPCR) and at protein level by enzyme-linked immunosorbent assay (ELISA) and western blotting analysis. RESULTS: A transient CAV1 knockdown in sfd-FLSs resulted in a decrease in the IL-1ß-induced CCL2 mRNA expression level vs non-transfected cells and cells transfected with non-targeting siRNA. The concentration of secreted CCL2 was not affected significantly. CONCLUSIONS: Our study demonstrates that CCL2 expression in sfd-FLSs is CAV1-dependent, but only at transcript level. As the function of CAV1 has not been unequivocally determined, more studies are needed to confirm the role of CAV1 in inflammatory processes related to RA.

Concentrations of SP-A and HSP70 are associated with polarization of macrophages in pleural effusions of non-small cell lung cancer.

Damage-associated molecular pattern (DAMP) molecules can initiate an immune response through Toll-like receptors (TLRs). DAMPs are released from cells as a response to the extracellular danger and can be by-products of tissue damage. In cancer microenvironment necrotic cells release debris which has potency to become DAMPs. Non-small cell lung cancer (NSCLC) is often accompanied by pleural effusion (PE), which contains a variety of DAMPs. Surfactant protein A (SP-A) and heat shock protein 70 (Hsp70) are important DAMPs in the respiratory tract. The aim of this study was to determine a correlation between SP-A or Hsp70 and development of PE in the course of NSCLC. Moreover, we aimed to determine relationships between DAMPs and certain humoral factors associated with formation and persistence of PE as well as pleural-residing macrophages. In 34 PE samples, we estimated concentration of SP-A, Hsp70, IL-6, IL-18, G-CSF, M-CSF, SCF, SDF1α, VEGF as well as the fraction of macrophages and their pattern of polarization. We have found correlations between the concentration of the SP-A and Hsp70 and the percentage of PE-derived macrophages, also between concentrations of SP-A and Hsp70, and cytokines which participate in inflammation and processes involved in remodeling of extracellular matrix (ECM). Our data indicate an important role of SP-A during the development of PE associated with NSCLC. We suggest that measurement of concentration level of SP-A can be helpful in the course of diagnosis of malignant PE associated with NSCLC.

Levels of EGF and VEGF in patients with primary and secondary Sjögren's syndrome.

BACKGROUND: Aberrant angiogenesis plays a role in the pathogenesis of Sjögren's syndrome (SS). OBJECTIVES: The aim of this study was to compare the levels of vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF) in stimulatory parotid saliva and in serum in healthy subjects (HS), patients with primary SS (pSS) and secondary SS (sSS) and to evaluate the expression of EGF, proangiogenic VEGF165 and antiangiogenic VEGF165 b mRNA isoforms. Additionally, we determined the salivary levels of serine/arginine splicing factor (SRSF1), which regulates VEGF165 and VEGF165 b expression. MATERIAL AND METHODS: The study comprised 34 women (16 with pSS and 18 with sSS) and healthy subjects for blood and saliva sampling. EGF and VEGF levels in saliva and serum and salivary SRSF1 levels were determined by enzyme-linked immunosorbent assay (ELISA). The expression of VEGF165 , VEGF165 b and EGF in peripheral blood mononuclear cells (PBMC) was evaluated by quantitative polymerase chain reaction (qPCR). RESULTS: There were no differences in the levels of EGF, VEGF, SRSF1 and in the expression of the EGF, VEGF165 and VEGF165 b between HS and SS patients, or between pSS and sSS patients. The salivary levels of VEGF165 and EGF were significantly higher in pSS, sSS and HS than serum levels. Levels of SRSF1 correlated positively with VEGF and EGF levels. Levels of EGF, VEGF and SRSF1 correlated with each other. CONCLUSIONS: The balance of VEGF isoforms is not disturbed in SS. Saliva is more sensitive for the detection of EGF and VEGF than serum, but salivary levels of those proteins are not representative for SS.