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ID PMID Title PublicationDate abstract
26151758 Genomic modulators of gene expression in human neutrophils. 2015 Jul 7 Neutrophils form the most abundant leukocyte subset and are central to many disease processes. Technical challenges in transcriptomic profiling have prohibited genomic approaches to date. Here we map expression quantitative trait loci (eQTL) in peripheral blood CD16+ neutrophils from 101 healthy European adults. We identify cis-eQTL for 3281 neutrophil-expressed genes including many implicated in neutrophil function, with 450 of these not previously observed in myeloid or lymphoid cells. Paired comparison with monocyte eQTL demonstrates nuanced conditioning of genetic regulation of gene expression by cellular context, which relates to cell-type-specific DNA methylation and histone modifications. Neutrophil eQTL are markedly enriched for trait-associated variants particularly autoimmune, allergy and infectious disease. We further demonstrate how eQTL in PADI4 and NOD2 delineate risk variant function in rheumatoid arthritis, leprosy and Crohn's disease. Taken together, these data help advance understanding of the genetics of gene expression, neutrophil biology and immune-related diseases.
26011013 The effect of maternal Inflammation on foetal programming of metabolic disease. 2015 Aug Maternal obesity during pregnancy increases the child's risk of developing obesity and obesity-related diseases later in life. Key components in foetal programming of metabolic risk remain to be identified; however, chronic low-grade inflammation associated with obesity might be responsible for metabolic imprinting in the offspring. We have therefore surveyed the literature to evaluate the role of maternal obesity-induced inflammation in foetal programming of obesity and related diseases. The literature on this topic is limited, so this review also includes animal models where maternal inflammation is mimicked by single injections with lipopolysaccharide (LPS). An LPS challenge results in an immunological response that resembles the obesity-induced immune profile, although LPS injections provoke a stronger response than the subclinical obesity-associated response. Maternal LPS or cytokine exposures result in increased adiposity and impaired metabolic homeostasis in the offspring, similar to the phenotype observed after exposure to maternal obesity. The cytokine levels might be specifically important for the metabolic imprinting, as cytokines are both transferable from maternal to foetal circulation and have the capability to modulate placental nutrient transfer. However, the immune response associated with obesity is moderate and therefore potentially weakened by the pregnancy-driven immune modulation, dominated by anti-inflammatory Treg and Th2 cells. We know from other low-grade inflammatory diseases, such as rheumatoid arthritis, that pregnancy can improve disease state. If pregnancy is also capable of suppressing the obesity-associated inflammation, the immunological markers might be less likely to affect metabolic programming in the developing foetus than otherwise implied.
25963062 Immunogenicity of biologic treatments for psoriasis: therapeutic consequences and the pote 2015 Aug The five biologic agents approved for the treatment of psoriasis-etanercept, infliximab, adalimumab, ustekinumab, and secukinumab-have been transformative in the clinical management of severe forms of the disease. However, a significant number of patients fail to respond to these agents or experience a loss of efficacy over time, which may be attributable to the development of antidrug antibodies (ADAs). Increasing evidence, primarily in the context of rheumatoid arthritis or other chronic inflammatory diseases, suggests that concomitant administration of methotrexate may prevent or diminish the development of ADAs, thereby improving response rates. However, methotrexate is infrequently coadministered with biologic agents in patients with psoriasis, and the potential benefits of this strategy in the context of psoriasis are largely unexplored. In this review, we discuss clinical studies regarding the development and consequences of antibodies targeting biologic agents used in the treatment of psoriasis and present key findings describing the potential role of methotrexate as an inhibitor of immunogenicity. We also discuss clinical considerations pertaining to the use of methotrexate as a tool to reduce immunogenicity, and encourage further investigation into potential techniques to optimize this treatment approach in patients with psoriasis.
25894789 Interleukin-17 in systemic lupus erythematosus: A comprehensive review. 2015 Systemic lupus erythematosus (SLE) is a complicated autoimmune disease of multifactorial pathoaetiology. One of the most serious manifestations is lupus nephritis. The pathogenesis of SLE has not been well elucidated, but it has been reported that interleukin-17 (IL-17) and Th17 cells play important roles in the pathogenesis of SLE. IL-17A, a member of IL-17 family, amplifies the immune response by inducing the local production of chemokines and cytokines, recruiting neutrophils and monocytes, augmenting the production of autoantibodies, and aggravating the inflammation and damage of target organs such as the kidney in SLE. In recent years, several IL-17A pathway inhibitors have advanced into clinical trials, including the anti-IL-17A monoclonal antibody and the anti-17RA monoclonal antibody. Several agents have shown great success in Phase II trials in multiple autoimmune diseases such as psoriasis, rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, and non-infectious uveitis, which has sparked the urgent need of anti-IL-17A as innovative therapeutic option in controlling disease activity of moderate-to-severe SLE. Here, we review and summarize current progress in IL-17A and SLE from in vitro studies, human expression studies, and animal models, providing novel insight into its therapeutic potential.
25829107 Characterization of biomimetic calcium phosphate labeled with fluorescent dextran for quan 2015 Jul Bone resorbing osteoclasts represent an important therapeutic target for diseases associated with bone and joint destruction, such as rheumatoid arthritis, periodontitis, and osteoporosis. The quantification of osteoclast resorptive activity in vitro is widely used for screening new anti-resorptive medications. The aim of this paper was to develop a simplified semi-automated method for the quantification of osteoclastic resorption using fluorescently labeled biomimetic mineral layers which can replace time intensive, often subjective and clearly non-sustainable use of translucent slices of tusks from vulnerable or endangered species such as the elephant. Osteoclasts were formed from RAW 264.7 mouse monocyte cell line using the pro-resorptive cytokine receptor activator of nuclear factor kappa-B ligand (RANKL). We confirmed that fluorescent labeling did not interfere with the biomimetic features of hydroxyapatite, and developed an automated method for quantifying osteoclastic resorption. Correlation between our assay and traditional manual measurement techniques was found to be very strong (R(2)=0.99). In addition, we modified the technique to provide depth and volume data of the resorption pits by confocal imaging at defined depths. Thus, our method allows automatic quantification of total osteoclastic resorption as well as additional data not obtainable by the current tusk slice technique offering a better alternative for high throughput screening of potential antiresorptives.
25576662 Fusobacterium nucleatum: a commensal-turned pathogen. 2015 Feb Fusobacterium nucleatum is an anaerobic oral commensal and a periodontal pathogen associated with a wide spectrum of human diseases. This article reviews its implication in adverse pregnancy outcomes (chorioamnionitis, preterm birth, stillbirth, neonatal sepsis, preeclampsia), GI disorders (colorectal cancer, inflammatory bowel disease, appendicitis), cardiovascular disease, rheumatoid arthritis, respiratory tract infections, Lemierre's syndrome and Alzheimer's disease. The virulence mechanisms involved in the diseases are discussed, with emphasis on its colonization, systemic dissemination, and induction of host inflammatory and tumorigenic responses. The FadA adhesin/invasin conserved in F. nucleatum is a key virulence factor and a potential diagnostic marker for F. nucleatum-associated diseases.
25380609 Impact of different etiologies of bronchiectasis on the pulmonary function tests. 2015 Mar BACKGROUND: Bronchiectasis develops along the natural course of several respiratory and systemic conditions and induces significant changes in the morphofunctional structure of airways. Our objective was to assess the impact of various causes of bronchiectasis on clinical data, pulmonary function tests, and high-resolution computed tomography (HRCT). METHODS: The present report was a cross-sectional study that was conducted with 112 consecutive patients with bronchiectasis, who were allocated to five groups, as follows: sequelae of tuberculosis, history of non-tuberculosis infection, cystic fibrosis (CF), primary ciliary dyskinesia (PCD), and rheumatoid arthritis. All of the participants underwent spirometry, whole-body plethysmography, measurement of the diffusing capacity for carbon monoxide (DLco), and HRCT. RESULTS: The highest HRCT score was exhibited in patients with CF (6.03 ± 1.03). The values of forced expiratory volume in 1 second (FEV1) (52.2 ± 17.7%) and DLco (74.1 ± 15.2%) were lower in patients with sequelae of tuberculosis. The increase in the residual volume was more accentuated in the patients with CF (193.5 ± 39.5%) and PCD (189 ± 36.4%). By the multivariate analysis, the cause of FEV1 and bronchiectasis, HRCT score, and degree of dyspnea behaved as independent predictors of DLco. CONCLUSION: In individuals with bronchiectasis, the pulmonary function abnormalities are associated with the etiology of the underlying disease.
25840040 Surgical and clinical efficacy of sacroiliac joint fusion: a systematic review of the lite 2015 Jul OBJECT: The sacroiliac joint (SIJ) and surgical intervention for treating SIJ pain or dysfunction has been a topic of much debate in recent years. There has been a resurgence in the implication of this joint as the pain generator for many patients experiencing low-back pain, and new surgical methods are gaining popularity within both the orthopedic and neurosurgical fields. There is no universally accepted gold standard for diagnosing or surgically treating SIJ pain. The authors systematically reviewed studies on SIJ fusion in the neurosurgical and orthopedic literature to investigate whether sufficient evidence exists to support its use. METHODS: A literature search was performed using MEDLINE, Google Scholar, and OvidSP-Wolters Kluwer Health for all articles regarding SIJ fusion published from 2000 to 2014. Original, peer-reviewed, prospective or retrospective scientific papers with at least 2 patients were included in the study. Exclusion criteria included follow-up shorter than 1-year, nonsurgical treatment, inadequate clinical data as determined by 2 independent reviewers, non-English manuscripts, and nonhuman subjects. RESULTS: A total of 16 peer-reviewed journal articles met the inclusion criteria: 5 consecutive case series, 8 retrospective studies, and 3 prospective cohort studies. A total of 430 patients were included, of whom 131 underwent open surgery and 299 underwent minimally invasive surgery (MIS) for SIJ fusion. The mean duration of follow-up was 60 months for open surgery and 21 months for MIS. SIJ degeneration/arthrosis was the most common pathology among patients undergoing surgical intervention (present in 257 patients [59.8%]), followed by SIJ dysfunction (79 [18.4%]), postpartum instability (31 [7.2%]), posttraumatic (28 [6.5%]), idiopathic (25 [5.8%]), pathological fractures (6 [1.4%]), and HLA-B27+/rheumatoid arthritis (4 [0.9%]). Radiographically confirmed fusion rates were 20%-90% for open surgery and 13%-100% for MIS. Rates of excellent satisfaction, determined by pain reduction, function, and quality of life, ranged from 18% to 100% with a mean of 54% in open surgical cases. For MIS patients, excellent outcome, judged by patients' stated satisfaction with the surgery, ranged from 56% to 100% (mean 84%). The reoperation rate after open surgery ranged from 0% to 65% (mean 15%). Reoperation rate after MIS ranged from 0% to 17% (mean 6%). Major complication rates ranged from 5% to 20%, with 1 study that addressed safety reporting a 56% adverse event rate. CONCLUSIONS: Surgical intervention for SIJ pain is beneficial in a subset of patients. However, with the difficulty in accurate diagnosis and evidence for the efficacy of SIJ fusion itself lacking, serious consideration of the cause of pain and alternative treatments should be given before performing the operation.
27965669 Complement Regulator FHR-3 Is Elevated either Locally or Systemically in a Selection of Au 2016 The human complement factor H-related protein-3 (FHR-3) is a soluble regulator of the complement system. Homozygous cfhr3/1 deletion is a genetic risk factor for the autoimmune form of atypical hemolytic-uremic syndrome (aHUS), while also found to be protective in age-related macular degeneration (AMD). The precise function of FHR-3 remains to be fully characterized. We generated four mouse monoclonal antibodies (mAbs) for FHR-3 (RETC) without cross-reactivity to the complement factor H (FH)-family. These antibodies detected FHR-3 from human serum with a mean concentration of 1 μg/mL. FHR-3 levels in patients were significantly increased in sera from systemic lupus erythematosus, rheumatoid arthritis, and polymyalgia rheumatica but remained almost unchanged in samples from AMD or aHUS patients. Moreover, by immunostaining of an aged human donor retina, we discovered a local FHR-3 production by microglia/macrophages. The mAb RETC-2 modulated FHR-3 binding to C3b but not the binding of FHR-3 to heparin. Interestingly, FHR-3 competed with FH for binding C3b and the mAb RETC-2 reduced the interaction of FHR-3 and C3b, resulting in increased FH binding. Our results unveil a previously unknown systemic involvement of FHR-3 in rheumatoid diseases and a putative local role of FHR-3 mediated by microglia/macrophages in the damaged retina. We conclude that the local FHR-3/FH equilibrium in AMD is a potential therapeutic target, which can be modulated by our specific mAb RETC-2.
27616144 Elevated serum levels of free interleukin-18 in adult-onset Still's disease. 2016 Dec OBJECTIVE: IL-18 is a pro-inflammatory cytokine of the IL-1 family that is naturally inhibited by IL-18 binding protein (IL-18BP). High levels of IL-18 have been described in the serum of adult-onset Still's disease (AOSD) patients, but only total IL-18 levels (including inactive IL-18 bound to IL-18BP) have been measured. With a specific immunoassay, we aimed to measure free IL-18 serum levels in AOSD patients and other rheumatic diseases. METHODS: An ELISA was developed to measure free IL-18. Its sensitivity and specificity were tested by spiking recombinant IL-18 or IL-18BP in serum and PBS supplemented with 5% BSA. The binding affinity of IL-18 to IL-18BP was calculated by titration experiments using the ELISA and by Biacore analysis. Sera of 37 AOSD patients and 138 controls (40 healthy controls, 30 RA, 29 SLE, 21 AS and 18 PsA) were assayed for free IL-18, IL-18BP, total IL-18 and other cytokines. Correlations were performed between free IL-18 and markers of disease activity in AOSD patients. RESULTS: Free IL-18 serum levels were significantly higher in AOSD patients (median 8.89 pg/ml) than in healthy and disease controls (1.37 pg/ml; P < 0.01). Free IL-18 serum levels correlated with AOSD activity. The affinity of IL-18 to IL-18BP was found to be much higher than previously described, with a dissociation constant ranging from 30 to 50 pM. CONCLUSION: Free IL-18 levels are specifically elevated in AOSD compared with other inflammatory diseases, suggesting that IL-18 represents a potential target for the treatment of AOSD.
27431344 Use of Biologics in Sjögren's Syndrome. 2016 Aug The management of patients suffering from primary Sjögren syndrome (pSS) has long been mainly symptomatic and demonstration of effectiveness of systemic drugs was lacking. However, progress made in the understanding of pSS pathogenesis has allowed moving into a more targeted approach to therapeutic intervention. Given the key role of chronic B-cell activation, B-cell target therapies were the first candidates. New pathways are currently being investigated, including costimulation and ectopic germinal center. In this review, we summarize the current evidence regarding B-cell targeted and anti-TNF therapies and provide an overview of promising drugs in the pipeline.
29309109 Case report of Mikulicz's disease: A modern concept of an old entity. 2016 Apr INTRODUCTION: Modern knowlegde defines Mikulicz´s disease as a part of immunoglobulin G4-related disease. The main feature is the presence of lymphoplasmacytic infiltrates, immunoglobulin G4 plasma cells positivity, distinctive storiform fibrosis and moderate eosinophilia. CASE REPORT: A 59-years old male presented with a mild keratoconjuctivitis sicca and enlarged lacrimal and salivary glands during the last two years. Althought clinical presentation of the patient was typical, earlier testing did not pinpoint Mikulicz ´s disease. By typical clinical presentation, elevated serum immunoglobulin G4 level and histopathological finding of lacrimal glands tissue we diagnosed Mikulicz´s disease successfully treated with corticosteroid therapy. CONCLUSION: We reported the first case of IgG4-related Mikulicz´s disease in Serbia. Our report highlights IgG4-related Mikulicz` s disease as an important differential diagnosis with Sjögren`s syndrome and lymphoproliferative disease in rheumatological practice.
24664458 The metalloproteinase ADAM17 and the epidermal growth factor receptor (EGFR) signaling dri 2015 May Primary Sjögren's syndrome (pSS) is a chronic autoimmune disorder that particularly compromises the function of exocrine glands. The pathogenetic mechanisms of this autoimmune exocrinopathy have not been fully elucidated. Since increasing evidence actually suggests that the epidermal growth factor receptor (EGFR) pathway has a major impact on the inflammatory/immune reactions of the epithelial cells, in the apparent effort of enhancing innate immune defense while opposing overactivation of pro-inflammatory functions, the focus of the work presented here is clarify whether the EGFR-extracellular-signal-regulated kinase (ERK) pathway plays a role in the pro-inflammatory responses mounted by pSS salivary gland epithelial cells (SGEC). Investigations revealed that the EGFR-mediated activation of the downstream effectors ERK1/2 in pSS SGEC appeared to require ADAM17-dependent release of the endogenous EGFR ligand amphiregulin and transactivation of the EGFR. Moreover, blockade of amphiregulin bioactivity using a neutralizing Ab significantly reduced EGFR transactivation and ERK1/2 phosphorylation. In addition, pSS SGEC treated with the specific ADAM17 inhibitor TAPI-1 and with the EGFR inhibitor AG1478 exhibited deactivated AREG/EGFR/ERK signaling pathway and reduced pro-inflammatory cytokines released.
27431353 New Treatment Guidelines for Sjögren's Disease. 2016 Aug Sjögren's disease is associated with a high burden of illness, diminished quality of life, and increased health care costs. The Sjögren's Syndrome Foundation developed the first US clinical practice guidelines for management of the oral, ocular, and rheumatologic or systemic manifestations. Guideline recommendations were reviewed by a consensus expert panel using a modified Delphi process. This initiative should improve the quality and consistency of care for Sjögren's disease in the United States, guide insurance reimbursement, and define areas for future study. Guidelines will be periodically reviewed and revised as new information becomes available.
27045581 Cytometry by time-of-flight immunophenotyping identifies a blood Sjögren's signature corr 2016 Jun BACKGROUND: Mass cytometry has recently emerged as a promising tool for clinical research. However, few studies have demonstrated its benefit for patient stratification and biomarker identification. Primary Sjögren's syndrome (pSS) is a prototype of chronic autoimmune disease, the pathogenesis of which remains unclear and for which treatment does not exist. OBJECTIVE: This observational case-control study was designed to discover new cellular biomarkers and therapeutic targets in patients with pSS. METHODS: Forty-nine patients with pSS and 45 control subjects were enrolled for clinical evaluation and mass cytometry quantification of 34 protein markers in blood. For a third of these subjects, matched labial salivary gland biopsy specimens were also analyzed by mass cytometry and immunohistochemistry. RESULTS: In salivary gland biopsy specimens from patients with pSS, we identified a high number of activated CD8(+) T cells, terminally differentiated plasma cells, and activated epithelial cells, pointing to new pathogenic mechanisms for future clinical intervention. In blood, we identified a 6-cell disease signature defined by decreased numbers of CD4 and memory B lymphocytes, decreased plasmacytoid dendritic cell numbers, and increased representation of activated CD4 and CD8 T cells and plasmablasts. These blood cellular components correlated with clinical parameters and, when taken together, clustered patients into subsets with distinct disease activity and glandular inflammation. CONCLUSION: This first application of mass cytometry to a well-stratified clinical cohort and small biopsy tissues establishes the benefits of such an approach for the discovery of new biomarkers and therapeutic targets. Similar high-dimensional immunophenotyping strategies could be implemented in longitudinal and interventional clinical settings in this and other disease areas.
26884645 Increased IL-21 Expression Induces Granzyme B in Peripheral CD5(+) B Cells as a Potential 2016 Recently, we reported elevated proportions of circulating follicular T helper cells and higher levels of interleukin- (IL-) 21 in primary Sjögren's syndrome (pSS). Interaction of invariant natural killer T (iNKT) cells with B cells and granzyme B (GrB) production may be also important in pSS. Thirty-two pSS patients and 24 healthy controls were enrolled in our study. We investigated the expression of intracellular GrB and IL-21 receptor (IL-21R) of CD19(+)CD5(+) and CD19(+)CD5(-) B cells; furthermore, we determined the IL-21 expression of iNKT cells as well. We also assessed the proportion of transitional (CD19(+)CD24(high)CD38(high)), mature (CD19(+)CD24(int)CD38(int)) and primarily memory (CD19(+)CD24(high)CD38(-)) B cells. CD5(+) but not CD5(-) B cells showed elevated GrB and IL-21R expression in pSS; additionally IL-21 expression of iNKT cells was also elevated. The ratios of transitional and mature B cells were elevated in pSS, while primarily memory B cell percentages were decreased, which correlated with GrB and IL-21R expression of CD19(+) B cells. Our results suggest that enhanced IL-21R expression of CD19(+)CD5(+) B cells and production of IL-21 by iNKT cells may play an important role in the pathogenesis of pSS by regulating CD19(+)CD5(+) B cell functions and increasing GrB production, presumably leading to a counter-regulatory effect in the disease.
26860322 Vitamin D and Its Relevance in the Etiopathogenesis of Oral Cavity Diseases. 2016 Oct Vitamin D belongs to a group of fat-soluble secosteroids which assume many roles in the human organism. In humans the most important forms are vitamin D3 and vitamin D2. Their primary function is the regulation of the calcium and phosphorus balance, which promote the growth of healthy bony tissue. Studies over the past few years have revealed a much wider role of vitamin D involving the aging processes, carcinogenesis, the carbohydrate balance as well as the effects on the course of various infections. In this paper we discuss the basic functions of vitamin D in the human body and the mechanisms of its activity and we summarize recent reports on the impact of vitamin D on the oral cavity with a special emphasis on autoimmunologic diseases, including: recurrent aphthous stomatitis, Behçet syndrome and Sjögren syndrome.
25963068 Primary Sjögren's syndrome and occupational risk factors: A case-control study. 2015 Jun OBJECTIVES: A case-control study was carried out to investigate the relation between primary Sjögren's syndrome (pSS) and occupational exposure. METHODS: One hundred seventy five cases of pSS followed up into the internal medicine departments of three French university hospitals from 2010 to 2013 were included. For each case, two age and gender matched controls were selected during the same period in the same departments. Occupational exposure was assessed retrospectively by industrial hygienists and occupational practitioners. Exposure to occupational factors such as organic solvents or silica was investigated using semiquantitative estimates of exposure. An exposure score was calculated for each subject based on probability, intensity, daily frequency, and duration of exposure for each period of employment. The final cumulative exposure score was obtained, taking into account all periods of employment. RESULTS: Significant associations with pSS were observed for dichloromethane (OR 9.28, 95%CI 2.60-33.03), perchlorethylene (OR 2.64, 95%CI 1.20-5.77) chlorinated solvents (OR 2.95, 95%CI 1.77-4.93), benzene (OR 3.30, 95%CI 1.07-10.26), toluene (OR 4.18 95%CI 1.41-12.43), white spirit (OR 3.60, 95%CI 1.39-9.33), aromatic solvents (OR 3.03, 95%CI 1.41-6.50) and any types of solvents (OR 2.76, 95%CI 1.70-4.47). Risk of pSS was significantly associated with a high cumulative exposure score of occupational exposure to toluene (OR 4.69, 95%CI 1.42-15.45), white spirit (OR 3.30, 95%CI 1.07-10.26), aromatic solvents (OR 2.50, 95%CI 1.06-5.91) and any types of solvents (OR 2.25, 95%CI 1.20-4.22). CONCLUSION: This work suggests the influence of occupational risk factors in the occurrence of pSS.
28300881 Frontal fibrosing alopecia in association with Sjögren's syndrome: more than a simple coi 2016 Sep Frontal fibrosing alopecia is a distinctive form of scarring alopecia considered to be a clinical variant of lichen planopilaris. It predominantly occurs in postmenopausal women and has a slowly progressive course. It was first described by Kossard in 1994. Since then the number of reported cases has increased significantly. Coexistence of frontal fibrosing alopecia and autoimmune disorders - such as discoid erythematosus lupus and Sjögren's syndrome - may suggest a common pathogenic background among the diseases.
27815483 Effect of Autologous Serum Eye Drops in Patients with Sjögren Syndrome-related Dry Eye: C 2016 11 AIM: To evaluate in vivo changes after therapy using autologous serum (AS) eye drops in Sjögren's syndrome (SS)-related dry eyes by confocal microscopy. PATIENTS AND METHODS: In this study, 24 patients with SS-related dry eyes [12 in AS eye drop therapy and 12 in artificial tear (AT) therapy] and 24 healthy volunteers were recruited. Ocular Surface Disease Index (OSDI), central corneal thickness, tear film, break-up time, corneal and conjunctival staining, Schirmer's test and corneal confocal microscopy were investigated. RESULTS: Tear production, tear stability, corneal staining, inflammation, and central corneal thickness, Langherans cells, activated keratocytes, intermediate epithelial cell density, nerve tortuosity, number of sub-basal nerve branches, and number of bead-like formations differed between patients and controls (p<0.0001). The AT and AS groups differed in the OSDI, number of branches, and number of beadings (p<0.0001). CONCLUSION: AS eye drops improve symptoms and confocal microscopy findings in SS-related dry eyes.