Presence Of Serum Autoantibodies Research Articles

Are seronegative patients with rheumatoid arthritis and clinically suspect arthralgia properly represented in randomized clinical trials?

Rheumatoid arthritis (RA) is a chronic immuno-inflammatory disease whose outcomes can vary greatly from one patient to another. One of the main prognostic factors is the presence of serum autoantibodies, such as rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPA). Indeed, when seropositive, patients with RA are at higher risk of radiographic progression, disability, and increased mortality. Moreover, while the introduction of the 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology (ACR/EULAR) classification criteria has allowed for an earlier diagnosis, studies on large early arthritis cohorts have also shown that these criteria are less capable of identifying seronegative patients, who are therefore at a higher risk of being diagnosed and treated late. In light of these, the major randomized controlled trials have mostly enrolled patients with autoantibody-positive disease. However, in recent years, it became evident that the two serotypes of RA differ significantly from many points of view. Alongside this, a greater understanding of the disease pathogenesis, particularly the presence of antibodies in patients' serum even before the onset of arthritis, has generated significant interest in exploring whether the disease could be prevented by treating patients in the pre-arthritis phases. Once again, emerging trials predominantly enroll subjects positive for RA autoantibodies, potentially overlooking seronegative individuals with arthralgia-at-risk.

The Effect of Simvastatin on Thyroid Function in Experimental Autoimmune Thyroiditis Induced in Rats

Autoimmune thyroiditis or Hashimoto’s thyroiditis (HT): is the most common autoimmune thyroid disease. is characterized by marked lymphocytic infiltration and the presence of serum autoantibodies against Thyroid peroxidase (TPO) and Thyroglobulin (TG). HT is a prevalent cause of hypothyroidism in areas of the world where dietary iodine is sufficient. Genetic predisposition and cellular and humoral immunity play a role in thyroid autoimmune pathogenesis. Antithyroid antibodies are produced by interaction between APC, T cells, and B cells to fix complement. Thyroid tissue is more severely damaged by complement-dependent antibody-mediated cytotoxicity. Statins, the powerful inhibitors of HMG-CoA reductase have pleotropic effects including anti-inflammatory and immunomodulatory effects. In this current study, Experimental autoimmune thyroiditis was induced in twenty-four female Wistar rat. Simvastatin was given at a dose of 4mg/kg for 30 days. Thyroid autoantibodies and Thyroid hormones were measured by ELISA technique Results showed that Simvastatin reduced autoantibodies against TPO and TG. It also lowered serum level of TSH and increased serum level of T4. Due to the undesirable side effects associated with the current treatment options used in Autoimmune thyroiditis. Simvastatin might be a promising approach in the treatment of this disease.

Serum autoantibodyome reveals that healthy individuals share common autoantibodies

SUMMARYAutoantibodies are a hallmark of both autoimmune disease and cancer, but they also occur in healthy individuals. Here, we perform a meta-analysis of nine datasets and focus on the common autoantibodies shared by healthy individuals. We report 77 common autoantibodies based on the protein microarray data obtained from probing 182 healthy individual sera on 7,653 human proteins and an additional 90 healthy individual sera on 1,666 human proteins. There is no gender bias; however, the number of autoantibodies increase with age, plateauing around adolescence. We use a bioinformatics pipeline to determine possible molecular-mimicry peptides that can contribute to the elicitation of these common autoantibodies. There is enrichment of intrinsic properties of proteins like hydrophilicity, basicity, aromaticity, and flexibility for common autoantigens. Subcellular localization and tissue-expression analysis reveal that several common autoantigens are sequestered from the circulating autoantibodies.

The Conundrum of Psoriatic Arthritis: a Pathogenetic and Clinical Pattern at the Midpoint of Autoinflammation and Autoimmunity.

Psoriatic arthritis (PsA) is a chronic inflammatory condition characterized by psoriasis, synovitis, enthesitis, spondylitis, and the possible association with other extra-articular manifestations and comorbidities. It is a multifaceted and systemic disorder sustained by complex pathogenesis, combining aspects of autoinflammation and autoimmunity. Features of PsA autoinflammation include the role of biomechanical stress in the onset and/or exacerbation of the disease; the evidence of involvement of the innate immune response mediators in the skin, peripheral blood and synovial tissue; an equal gender distribution; the clinical course which may encounter periods of prolonged remission and overlapping features with autoinflammatory syndromes. Conversely, the role of autoimmunity is evoked by the association with class I major histocompatibility complex alleles, the polyarticular pattern of the disease which sometimes resembles rheumatoid arthritis and the presence of serum autoantibodies. Genetics also provide important insights into the pathogenesis of PsA, particularly related to class I HLA being associated with psoriasis and PsA. In this review, we provide a comprehensive review of the pathogenesis, genetics and clinical features of PsA that endorse the mixed nature of a disorder at the crossroads of autoinflammation and autoimmunity.

Presence of autoantibodies in serum does not impact the occurrence of immune checkpoint inhibitor-induced hepatitis in a prospective cohort of cancer patients

PurposeImmune checkpoint inhibitor (ICI)-induced hepatitis belongs to the frequently occurring immune-related adverse events (irAEs), particularly with the combination therapy involving ipilimumab and nivolumab. However, predisposing factors predicting the occurrence of ICI-induced hepatitis are barely known. We investigated the association of preexisting autoantibodies in the development of ICI-induced hepatitis in a prospective cohort of cancer patients.MethodsData from a prospective biomarker cohort comprising melanoma and non-small cell lung cancer (NSCLC) patients were used to analyze the incidence of ICI-induced hepatitis, putatively associated factors, and outcome.Results40 patients with melanoma and 91 patients with NSCLC received ICI between July 2016 and May 2019. 11 patients developed ICI-induced hepatitis (8.4%). Prior to treatment, 45.5% of patients in the hepatitis cohort and 43.8% of the control cohort showed elevated titers of autoantibodies commonly associated with autoimmune liver diseases (p = 0.82). We found two nominally significant associations between the occurrence of ICI-induced hepatitis and HLA alleles associated with autoimmune liver diseases among NSCLC patients. Of note, significantly more patients with ICI-induced hepatitis developed additional irAEs in other organs (p = 0.0001). Neither overall nor progression-free survival was affected in the hepatitis group.ConclusionWe found nominally significant associations of ICI-induced hepatitis with two HLA alleles. ICI-induced hepatitis showed no correlation with liver-specific autoantibodies, but frequently co-occurred with irAEs affecting other organs. Unlike other irAEs, ICI-induced hepatitis is not associated with a better prognosis.

Dysfunctional Immune Regulation in Autoimmune Hepatitis: From Pathogenesis to Novel Therapies.

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by hypergammaglobulinemia, presence of serum autoantibodies and histological features of interface hepatitis. AIH therapeutic management still relies on the administration of corticosteroids, azathioprine and other immunosuppressants like calcineurin inhibitors and mycophenolate mofetil. Withdrawal of immunosuppression often results in disease relapse, and, in some cases, therapy is ineffective or associated with serious side effects. Understanding the mechanisms underlying AIH pathogenesis is therefore of paramount importance to develop more effective and well tolerated agents capable of restoring immunotolerance to liver autoantigens. Imbalance between effector and regulatory cells permits liver damage perpetuation and progression in AIH. Impaired expression and regulation of CD39, an ectoenzyme key to immunotolerance maintenance, have been reported in Tregs and effector Th17-cells derived from AIH patients. Interference with these altered immunoregulatory pathways may open new therapeutic avenues that, in addition to limiting aberrant inflammatory responses, would also reconstitute immune homeostasis. In this review, we highlight the most recent findings in AIH immunopathogenesis and discuss how these could inform and direct the development of novel therapeutic tools.

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Neurological Entity?

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disorder of unknown physiopathology with multisystemic repercussions, framed in ICD-11 under the heading of neurology (8E49). There is no specific test to support its clinical diagnosis. Our objective is to review the evidence in neuroimaging and dysautonomia evaluation in order to support the neurological involvement and to find biomarkers serving to identify and/or monitor the pathology. The symptoms typically appear acutely, although they can develop progressively over years; an essential trait for diagnosis is “central” fatigue together with physical and/or mental exhaustion after a small effort. Neuroimaging reveals various morphological, connectivity, metabolic, and functional alterations of low specificity, which can serve to complement the neurological study of the patient. The COMPASS-31 questionnaire is a useful tool to triage patients under suspect of dysautonomia, at which point they may be redirected for deeper evaluation. Recently, alterations in heart rate variability, the Valsalva maneuver, and the tilt table test, together with the presence of serum autoantibodies against adrenergic, cholinergic, and serotonin receptors were shown in a subgroup of patients. This approach provides a way to identify patient phenotypes. Broader studies are needed to establish the level of sensitivity and specificity necessary for their validation. Neuroimaging contributes scarcely to the diagnosis, and this depends on the identification of specific changes. On the other hand, dysautonomia studies, carried out in specialized units, are highly promising in order to support the diagnosis and to identify potential biomarkers. ME/CFS orients towards a functional pathology that mainly involves the autonomic nervous system, although not exclusively.

Response of peripheral blood basophils in subjects with chronic spontaneous urticaria during treatment with omalizumab

Treatment of patients with asthma or food allergy with omalizumab results in several consistent changes in circulating basophils. The multiple basophil phenotypes observed in patients with chronic spontaneous urticaria (CSU) present some unique attributes that may not respond in a similar fashion to patients with asthma or food allergy. As part of a clinical study on the therapeutic outcomes of omalizumab treatment in CSU, the basophil compartment was examined for changes in characteristics predicted by prior studies. This study sought to examine the changes in basophil function and its relationship to auto-antibodies in serum during treatment with omalizumab. At multiple time points before and during omalizumab treatment of patients with CSU, basophil surface IgE and FcεRI expression, cellular spleen tyrosine kinase (SYK) expression, IgE-mediated histamine release (HR), and the presence of auto-antibodies in serum were determined. Three basophil phenotypes were enumerated in the clinical study and used to group results in this basophil study: subjects with (1) basopenia, (2) normal basophil numbers with normal IgE-mediated HR, and (3) normal basophil numbers with poor HR. Basopenia was highly associated with the presence of auto-antibodies to unoccupied FcεRI and basophil numbers did not change during treatment. Likewise, subjects who are basopenic showed no changes in SYK expression or HR during treatment. In basophils of subjects who are nonbasopenic, increases in SYK expression and HR showed the expected inverse relationship to starting SYK and HR levels. Treatment with omalizumab resulted in similar kinetics for decreases in surface FcεRI and IgE in all 3 groups. A unifying interpretation of the results revolves around the presence of auto-antibodies to FcεRI in CSU. If present, basopenia and an absence of changes in basophils during omalizumab treatment are observed. If auto-antibodies are absent, the changes in the basophil compartment are consistent with prior studies of asthma and food allergy. These group differences also are related to efficacy of the treatment for clinical outcomes, as found in the parent clinical study.

An Overview of Various Diagnostic Methods to Detect Antinuclear Antibodies of Connective Tissue Diseases

Antinuclear Antibodies (ANA) are present in many autoimmune disorders and these disorders are collectively called as Connective Tissue Diseases (CTD). There are various CTDs which includes Systemic Lupus Erythematosus (SLE), Sjogren’s syndrome, Systemic Sclerosis (SS), Inflammatory Myositis (IM), Mixed Connective Tissue Disorder (MCTD) and Rheumatoid Arthritis (RA). Detection of ANAs in these CTDs is highly sensitive and is of utmost importance. The ANAs specific to SLE includes anti-double stranded Deoxyribonucleic Acid (anti-dsDNA), single stranded DNA (ssDNA). Scleroderma or Systemic Sclerosis (SS) is an immune mediated rheumatic disease where autoantibodies like topoisomerase 1, Ribonucleic Acid (RNA) polymerase 1 and fibrillarin are useful in diagnosis. Idiopathic Inflammatory Myositis (IIM) such as polymyositis and dermatomyositis are characterised by the presence of autoantibodies like PM-scl (Polymyositis-Scleromyositis), Mi-1 (Myositis specific autoantibody found in idiopathic inflammatory myositis), Mi-2 and Ku (DNA Binding Protein in dermatomyositis). Antibody titres against polypeptides on the U1 Ribonucleoprotein (U1RNP) is useful in the detection mixed CTD. Sjogren’s syndrome is characterised by the presence of serum autoantibodies against two ribonucleoproteinic complexes like Ro/SSA (Extractable nuclear antigen found in Sjogren's syndrome related antigen A auto antibodies) and La/SSB (Extractable nuclear antigen found in Sjogren's syndrome or lupus erythematous). ANA analysis can be done by techniques like indirect immunofluorescence method, Enzyme Linked Immuno Sorbent Assay (ELISA), Immunoprecipitation in agar and western blotting. All these diagnostic methods give precise identification of these antibodies with high accuracy. Farr assay, Multiplex Immunoassay (MIA), Flow cytometry, antigen microarray is also gaining importance in the diagnosis of ANAs. The objective of this study was to discuss various methods of ANA testing so that the clinicians know its relevance in diagnosis. Certain advancement in the diagnosis of ANA is also included in this review.

Skeletal muscle redox signaling in rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovitis and the presence of serum autoantibodies. In addition, skeletal muscle weakness is a common comorbidity that contributes to inability to work and reduced quality of life. Loss in muscle mass cannot alone account for the muscle weakness induced by RA, but instead intramuscular dysfunction appears as a critical factor underlying the decreased force generating capacity for patients afflicted by arthritis. Oxidative stress and associated oxidative post-translational modifications have been shown to contribute to RA-induced muscle weakness in animal models of arthritis and patients with RA. However, it is still unclear how and which sources of reactive oxygen and nitrogen species (ROS/RNS) that are involved in the oxidative stress that drives the progression toward decreased muscle function in RA. Nevertheless, mitochondria, NADPH oxidases (NOX), nitric oxide synthases (NOS) and phospholipases (PLA) have all been associated with increased ROS/RNS production in RA-induced muscle weakness. In this review, we aim to cover potential ROS sources and underlying mechanisms of oxidative stress and loss of force production in RA. We also addressed the use of antioxidants and exercise as potential tools to counteract oxidative stress and skeletal muscle weakness.

Association between positivity of serum autoantibodies and liver disease severity in patients with biopsy-proven NAFLD

Background and aimsSome previous studies reported serum autoantibody positivity in patients with nonalcoholic fatty liver disease (NAFLD). The clinical significance of these findings remains uncertain. We aimed to investigate the association between the presence of serum autoantibodies and liver disease severity in NAFLD. Methods and resultsA total of 388 consecutive patients with biopsy-proven NAFLD were included in the study. Various serum autoantibodies (including also anti-nuclear antibodies [ANA]) were detected by indirect immunofluorescent or immunoblotting assays. Overall, 84 (21.6%) patients with biopsy-confirmed NAFLD had positivity for at least one of the measured serum autoantibodies. ANA positivity was present in 50 (12.9%) patients, whereas anti-U1RNP or pANCA antibodies were detectable in 9 (2.3%) and 6 (1.5%) patients, respectively. Multivariate logistic regression analysis showed that ANA positivity (adjusted-odds ratio: 4.51, 95%CI: 1.77–11.5; P = 0.002) or positivity of any serum autoantibodies (adjusted-odds ratio: 3.14, 95%CI: 1.30–7.62; P = 0.01) were independently associated with advanced liver fibrosis (stages F3–F4). In serum autoantibody/ANA-positive patients, the proportion of those with advanced fibrosis was also greater among carriers of PNPLA3 rs738409 GG or CG than among those carrying PNPLA3 rs738409 CC genotype. ConclusionsSerum autoantibody positivity was independently associated with advanced liver fibrosis in patients with biopsy-proven NAFLD. The presence of serum autoantibodies in patients with advanced fibrosis occurred more frequently amongst those carrying PNPLA3 rs738409 GG or CG genotypes.

Nutritional condition and gastrointestinal symptoms in patients with systemic sclerosis

Systemic sclerosis (scleroderma/SSc) is a rare, connective autoimmune multisystem disease with wide-reaching consequences. SSc is recognized by the presence of serum autoantibodies and fibroproliferative changes in the microvasculature which, in turn, results in too much accumulation of collagen fibres in the skin and internal organs. Gastrointestinal (GI) involvement is highly prevalent among SSc patients (seen in over 90% of cases). Altered GI function and subsequent nutritional disorders are common outcomes of SSc, affecting the quality of life (QoL) and possibly carrying an associated rate of morbidity and mortality. Disease-related malnourishment is also considered to have a detrimental effect on clinical outcomes. There is little information on dietary advice for SSc patients, and as GI complaints are risk factors for bad nutritional status, perceptive assessment seems to be necessary. As the SSc pathogenesis is yet to be explored, recent investigations have aimed to evaluate the effect of diet in terms of triggering or altering the course of the disease. The present review aimed to discuss current knowledge relating to the effect of nutrition on SSc pathogenesis.

Association of serum anti-centromere protein F antibodies with clinical response to infliximab in patients with rheumatoid arthritis: A prospective study

BackgroundOne-third of rheumatoid arthritis (RA) patients demonstrate no clinical improvement after receiving tumor necrosis factor inhibitors (TNFi). The presence of serum autoantibodies is a hallmark in RA and may provide information on future response to treatment. The aim of this prospective study was to search for novel serum autoantibodies useful to predict clinical response to TNFi. MethodsThe autoantibody repertoire was profiled on RA patients treated with TNFi as a first line of biologic therapy (N = 185), who were recruited in three independent cohorts. The presence and levels of autoantibodies in serum at baseline were analysed in association with the clinical response after 24 weeks follow-up. A multiplex bead array built using antigens selected from an initial untargeted screening was employed to identify the autoantibodies on a discovery cohort (N = 50) and to verify and validate the results on verification (N = 61) and validation (N = 74) cohorts. Non-parametric tests, meta-analysis and Receiver Operating Curves (ROC) were performed in order to assess the clinical relevance of the observed findings. ResultsNovel autoantibodies were associated with the clinical response to TNFi, showing different reactivity profiles among the different TNFi. The baseline levels of IgG antibodies against Centromere protein F (CENPF), a protein related to cell proliferation, were significantly (p<0.05) increased in responders (N = 111) to infliximab (IFX) compared to non-responders (N = 44). The addition of anti-CENPF antibodies to demographic and clinical variables (age, sex, DAS28-ESR) resulted in the best model to discriminate responders, showing an area under the curve (AUC) of 0.756 (95% CI [0.639–0.874], p = 0.001). A further meta-analysis demonstrated the significant association of anti-CENPF levels with the patient's subsequent response to IFX, showing a standardized mean difference (SMD) of -0.65 (95% CI [-1.02;-0. 27], p = 0.018). ConclusionsOur study reveals for the first time the potential of circulating anti-CENPF antibodies to predict the clinical response to IFX before starting the treatment. This finding could be potentially useful to guide therapeutic decisions and may lead to further studies focusing on the role of CENPF on RA pathology.

Gene silencing of extracellular matrix protein 1 (ECM1) results in phenotypic alterations of dermal fibroblasts reminiscent of clinical features of lichen sclerosus

BackgroundLichen sclerosus (LS) is an acquired inflammatory mucocutaneous disease affecting the anogenital area, characterized histologically by hyalinosis and thickened vessel walls in the dermis. The presence of serum autoantibodies against extracellular matrix protein 1 (ECM1) in LS patients may suggest its involvement in disease pathogenesis. ObjectiveTo examine if reduced ECM1 production by dermal fibroblasts contributes to the pathogenic features of LS. MethodsGene expression in ECM1 knockdown human dermal fibroblasts was analyzed by cDNA microarray. Functional enrichment for genes involved in cellular functions was conducted. Protein expression was analyzed by ELISA and confocal laser scanning microscopy using LS skin. ResultsMicroarray analysis identified 3035 differentially expressed genes in ECM1 knockdown cells, wherein 1471 were upregulated genes related exclusively to cell adhesion, proliferation, apoptosis, intracellular signaling, and extracellular matrix organization. Further narrowing with criteria specific for localization and function of ECM1 identified 48 upregulated genes identified to have structural, fibrogenic, and carcinogenic properties. Of these, laminin-332 and collagen-IV displayed altered immunolabeling within the basement membrane zone (BMZ) and dermal vessels in LS skin, similar to that of collagen-VII, which exhibited unchanged transcription levels in ECM1-knockdown fibroblasts. Collagen-VII bound to recombinant ECM1 in a solid-phase immunoassay and colocalized with ECM1 in the skin BMZ. Further, ECM1-knockdown fibroblasts exhibited a marked delay in cell migration and gel contraction. ConclusionIn the absence of ECM1 expression in fibroblasts there is selective dysregulation and disassembly of structural and extracellular matrix molecules, which may result in microstructural abnormalities reminiscent of LS.

Aryl hydrocarbon receptor inhibition and non-canonical signaling activation impact Treg function in autoimmune hepatitis

Abstract Treg are dysfunctional in autoimmune hepatitis (AIH), a severe hepatopathy characterized by hypergammaglobulinemia, presence of serum autoantibodies and interface hepatitis on histology. AIH-derived Treg display impaired expression of CD39, an ectonucleotidase that scavenges extracellular ATP to generate immunosuppressive adenosine. CD39 can be regulated upon activation of aryl-hydrocarbon-receptor (AHR), a mediator of toxin responses that also modulates T-cell immunity. Upon binding to endogenous or exogenous ligands, AHR dimerizes with aryl-hydrocarbon-receptor-nuclear-translocator (ARNT) or other non-canonical factors like estrogen-receptor-alpha (Era) or Kruppel-like-factor-6 (KLF6) to modulate gene expression. AHR is in turn regulated by the aryl-hydrocarbon-receptor-repressor (AHRR) that inhibits the transcriptional activity of the AHR/ARNT complex. We note that, compared to healthy subjects (HS), Treg obtained from AIH patients display increased AHRR levels and heightened expression of non-canonical binding factors Era and KLF6, but comparable AHR and ARNT levels. Differently from HS, AIH Treg do not upregulate CD39 expression and activity upon exposure to the AHR ligands unconjugated bilirubin (UCB), L-Kynurenine and quercetin. Silencing of AHRR and Era via siRNA boosts CD39 in AIH Treg in the presence of UCB and quercetin. We further note that, in AIH Treg, AHR binds Era with higher affinity than ARNT. In conclusion, multiple AHR signaling alterations might impact CD39 and Treg function in AIH. Targeted blockade of AHRR and Era represents a potential therapeutic approach to restore immune homeostasis in AIH and other chronic inflammatory conditions by boosting CD39.

Influence of reproductively significant autoantibodies on the quality of oocytes, obtained embryos and the chances of implantation in Assisted Reproductive Technologies cycles. Literature review

There is evidence suggesting that autoimmune mechanisms may influence fertility, manifesting as infertility or pregnancy loss. Numerous autoimmune diseases, including but not limited to systemic lupus erythematosus, anti-phospholipid syndrome and Hashimoto thyroiditis may be associated with infertility and pregnancy loss through different putative mechanisms. It is notable that fertility may be impaired in the presence of serum autoantibodies regardless of the presence of a clinically overt autoimmune disease. Autoimmunity may affect all stages of fertility via ovarian failure, implantation failure, and pregnancy loss. This review article will illustrate and discuss the available data on the link between chances of achieving pregnancy through Assisted Reproductive Technologies in real clinical setting in the presence of several autoantibodies affecting female reproductive system. Summarizing the available data from the world literature, it can be concluded that necessity exist in development of a reproductively significant antibodies line in application to direct, cross-over and cumulative assessment of the role of autoimmune antibodies carriage in the implementation of reproductive failures,bearing in mind new approaches to the strategy of overcoming autoimmune reproductive failure.

Systemic activation of B and CD4 but not CD8 cells drives early disease in lupus prone mice, while macrophages, CD4 and CD8 cells infiltrate the kidney with the exclusion of B cells

Abstract Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by the presence of autoantibodies in serum and multi-organ inflammation. Immune complex deposition in kidney can lead to lupus nephritis, which is a major risk factor for morbidity and mortality in SLE. Using FcγRIIB−/− mice as a lupus animal model, we performed a detailed time course analysis of the extent of the spontaneous leukocyte activation and expansion in spleen and in renal, inguinal, mesenteric lymph nodes. We then correlated the data with the onset of pathology and leukocyte infiltration in the kidney. In the FcγRIIB−/− mouse model, effector-memory CD4 cells and germinal centers appeared first in the spleen and renal lymph nodes, but not in other immune organs such as inguinal or mesenteric lymph nodes. As the disease progresses in these mice, lymphocytes undergo an extensive expansion that involves all immune organs in a systemic manner. At the same moment we can detect the first signs of kidney pathology, measured by histopathology and by the levels of creatinine and albumin in urine. In FcγRIIB−/− mice, the onset of kidney pathology correlates with leukocyte infiltration in kidney, detected both by parenchyma-restricted flow cytometry and histopathology. Macrophages, CD4 and CD8 cells are found both in glomerular and interstitial spaces with the exclusion of B cells, most likely suggesting a role for T cells and/or macrophage specific chemokine signals in lupus nephritic kidney.

Hypercoagulopathy and dento-alveolar surgery: a case of exodontia in a patient with hughes' syndrome

Antiphospholipid syndrome is a thrombophilic disorder in which the presence of serum autoantibodies to phospholipid causes disruption of the protein C antithrombotic pathway. Deposition of these autoantibodies in small blood vessels can lead to intimal hyperplasia and acute thromboses. The associated hypercoagulopathy is problematic in dentistry since, if proper haemostasis is not achieved prior to discharge of exodontia patients, excessive haematoma formation may result. This case report and review of the literature discusses the condition in the context of hypercoagulation with reference to a patient undergoing a simple extraction, and suffering post-operative complications amounting to a large haematoma requiring evacuation. CPD/Clinical Relevance: Post-operative bleeding is one of the most common complications of exodontia. This case report and review of the literature provides the reader with a concise summary of the clotting cascade in parallel with an unusual case of post-operative bleeding.

A case for IL-6, IL-17A, and nitric oxide in the pathophysiology of Sjögren’s syndrome

Sjögren's syndrome (SS) is an autoimmune epithelitis characterized by mononuclear cell (MNC) infiltration of the lacrimal and salivary glands (SG), as well as the presence of serum autoantibodies. This condition is a growing public health concern in Algeria. Herein, we sought to determine if the levels of interleukin (IL)-6, IL-17A, and nitric oxide (NO), were correlated with the extent of MNC infiltration. The expression of inducible NO synthase (NOS2) and CD68 was measured in the SG of all patients, but not in those of the normal controls (NCs). We included 44 primary Sjögren's syndrome (pSS) patients and 15 NCs in this study; we found that the expression of NOS2 and CD68 was elevated in all of the SG of SS patients. Additionally, the serum and saliva levels of IL-6, IL-17A, and NO were higher in the pSS patients, compared with the NCs. Furthermore, the NOS2-induced excess NO was associated with the extent of the MNC infiltration, and thereby with tissue injury. It is also important to note that there were correlations between the levels of IL-6, IL-17A, and NO. Such findings indicate that through the effects of NO, IL-17A participates in the pathophysiology of the disease. With the purpose of improving both the diagnosis and prognosis, IL-6, IL-17A, and NO should be assayed in the serum and saliva of patients suspected of SS.

Analysis of immunological profile, clinical features and response to treatment in pemphigus.

Pemphigus is an autoimmune disease, characterized by the presence of serum autoantibodies against Desmoglein (Dsg) 1 and 3. It can affect the skin and/or the mucous membranes. Some authors found a correlation between the serum levels of autoantibodies, disease activity and clinical phenotype of pemphigus. Anti Dsg1 autoantibodies appear related to cutaneous phenotype, anti Dsg3 autoantibodies to mucosal involvement. From 2011 to 2014, in patients with pemphigus, the serum levels of anti-Dsg1 and 3 antibodies were determined with enzyme-linked immuno-sorbent assay at diagnosis and after 6 months of different therapies. The correlations between levels of autoantibodies, clinical phenotype, clinical activity and response to therapy, were investigated. Thirty-five patients were included. Clinical phenotypes were: mucosal in 17 patients; mucous-cutaneous in 11; and cutaneous in 7. The status of anti-Dsg1 autoantibodies was significantly related to the cutaneous and mucous-cutaneous phenotypes both at diagnosis and after 6 months. The status of anti-Dsg3 autoantibodies was significantly related to the mucosal and mucous-cutaneous phenotypes only at first evaluation. No significant correlations were found between disease activity and the status of autoantibodies. No significant variations of autoantibody levels (between first and second sample) were found with regard to different therapies, except for the variation of anti-Dsg1 autoantibodies in one patient treated with systemic steroids and methotrexate. A correlation between serum levels of autoantibodies and clinical phenotype was found. Further studies over a longer follow-up period may better characterize the correlation between autoantibody levels, clinical activity and response to different therapies of pemphigus.