Single-cell transcriptomic profiling reveals a pathogenic role of cytotoxic CD4+ T cells in giant cell arteritis.

Giant cell arteritis (GCA) is a systemic vasculitis mediated by an aberrant immunological response against the blood vessel wall. Although the pathogenic mechanisms that drive GCA have not yet been elucidated, there is strong evidence that CD4+ T cells are key drivers of the inflammatory process occurring in this vasculitis. The aim of this study was to further delineate the role of CD4+ T cells in GCA by applying single-cell RNA sequencing and T cell receptor (TCR) repertoire profiling to 114.799 circulating CD4+ T cells from eight GCA patients in two different clinical states, active and in remission, and eight healthy controls. Our results revealed an expansion of cytotoxic CD4+ T lymphocytes (CTLs) in active GCA patients, which expressed higher levels of cytotoxic and chemotactic genes when compared to patients in remission and controls. Accordingly, differentially expressed genes in CTLs of active patients were enriched in pathways related to granzyme-mediated apoptosis, inflammation, and the recruitment of different immune cells, suggesting a role of this cell type in the inflammatory and vascular remodelling processes occurring in GCA. CTLs also exhibited a higher clonal expansion in active patients with respect to those in remission. Drug repurposing analysis prioritized maraviroc, which targeted CTLs, as potentially repositionable for this vasculitis. In addition, effector regulatory T cells (Tregs) were decreased in GCA and showed lower expression of genes involved in their suppressive activity. These findings provide further insights into the pathogenic role of CD4+ T cells in GCA and suggest targeting CTLs as a potential therapeutic option.

Lymphoid interstitial pneumonia in a patient with systemic lupus erythematosus: Case report and literature review.

Lymphoid interstitial pneumonia (LIP) is a rare form of interstitial pulmonary disease, which has been described in association with a wide range of autoimmune disorders. Although the association of this entity with Sjogren's syndrome is well known, only a few cases are reported in relation to systemic lupus erythematosus (SLE). The aim of this paper is to review the cases reported in literature to date, as well as to describe the characteristics of these patients including the new case presented herein. We will be focusing on the case of a 36-year-old female patient diagnosed with SLE on hydroxychloroquine treatment who develops pleuritic chest pain and progressive dyspnea after 3 years of follow-up. The chest CT scan showed pleural thickening and both multiple and bilateral micronodules. A lung biopsy was also performed, revealing an infiltration of lymphocytes, plasma cells, and histiocytes in the alveolar septa suggestive of LIP. After conducting a review of the literature, we identified seven other cases describing SLE in association with LIP. The majority of them were young women, and LIP tends to appear early in the course of the disease, even as a form of initial presentation in some cases. Symptoms included cough, dyspnea, and pleuritic pain, with the exception of one case which was asymptomatic. It is noteworthy that half of the patients were positive for anti-SSA/anti-SSB autoantibodies, and some of them also met criteria for Sjogren's syndrome. Treatment with steroids and other immunosuppressive agents improved symptoms in all of them.

Adherence to antimalarials and glucocorticoids treatment and its association with self-reported disease activity in systemic lupus erythematosus patients.

OBJECTIVES: We aimed to investigate the rate of non-adherence to antimalarials and glucocorticoids (GCs) and to analyze their potential relationships with sociodemographic characteristics, disease activity and accumulate damage in a cohort of Systemic lupus erythematosus (SLE) patients. METHODS: A cross-sectional study was conducted among 670 patients. The Systemic Lupus Erythematosus Activity Questionnaire (SLAQ) and the Lupus Damage Index Questionnaire (LDIQ) were used to assess disease activity and accumulated damage. RESULTS: The prevalence of non-adherence to antimalarials and GCs were 10.67% and 39.61%. 86.9% of participants indicated that the reason for stopping therapy was the presence of side effects. SLE patients with non-adherence to antimalarials and GCs had significantly higher scores in disease severity (SLAQ) compared to adherence patients (5.03 (2.12) vs 4.39 (2.61); p = .004 and (4.75 (2.29) vs 4.05 (2.78); p ≤ .001). CONCLUSION: Adherence to the treatment indicated in SLE differs from drug to drug. Findings highlight the importance of developing interventions to support adherence and improve outcomes among patients.

Psychological and quality of life effects of vaccination against COVID-19 in patients with systemic autoimmune diseases.

To verify the psychological and quality of life benefits of vaccination against COVID-19 in patients with systemic autoimmune diseases. In this study, levels of psychological stress, psychopathological symptoms, quality of life, and satisfaction with life were compared in patients with systemic autoimmune diseases vaccinated against COVID-19 (n = 132) versus unvaccinated patients (n = 254). To this end, we used the Perceived Stress Scale (PSS), Symptom Checklist-90-Revised (SCL-90-R), EUROQoL-5Q health questionnaire, and Satisfaction with Life Scale (SWLS), respectively. Statistically significant differences were found with better scores in the vaccinated group in the following quality of life dimensions: mobility (p ≤ 0.010), domestic activities (p ≤ 0.004), pain/discomfort (p ≤ 0.001), and anxiety/depression (p≤ 0.005). The scores were also significantly higher in the vaccinated group for the total values of quality of life (p ≤ 0.001), health status self-assessment on the EUROQoL-5Q (p ≤ 0.043), and satisfaction with life (p ≤ 0.015). In addition, the unvaccinated group presented higher scores with clinically pathological levels in depression and psychoticism for somatizations (p ≤ 0.006), depression (p ≤ 0.015), anxiety (p ≤ 0.003), and phobic anxiety (p ≤ 0.001). Finally, participants vaccinated with the complete regimen showed better levels of psychological well-being than those who were not vaccinated or those that had not completed the vaccination regimen. Our results reflect and confirm the positive effects reported elsewhere of the COVID-19 vaccine in autoimmune patients with systemic diseases, both in terms of quality and satisfaction with life as well as psychopathological symptoms and perceived stress. These benefits increased as the patients completed their vaccination schedule.

COVID-19 vaccine literacy in patients with systemic autoimmune diseases.

COVID-19 related infodemic is a threat to the successful COVID-19 vaccination campaigns. This might be especially apparent for patients with autoimmune diseases since there is no data available about the balance between benefits and risks of the newly developed COVID-19 vaccines in this population. We aim (i) to evaluate vaccine literacy skills in a population of patients with systemic autoimmune diseases, (ii) to examine the potential associations between vaccine literacy skills and sociodemographic characteristics and (iii) to analyze the relationships between attitudes, perceptions and beliefs about current vaccinations and vaccine literacy skills and sociodemographic characteristics. A cross-sectional study was conducted among 319 patients with systemic autoimmune diseases (92% females; 49.5% of patients in the 31-50 years age category). The vaccine literacy levels were determined using the Health Literacy about Vaccination in adulthood in Italian (HLVa-IT). Sociodemographic characteristics including gender, age, country and area of residence, civil status, socioeconomic status, educational attainment and occupational status were evaluated. The mean vaccine literacy functional and interactive-critical scores were 2.59 ± 0.74 and 3.07 ± 0.60, respectively. The vaccine literacy interactive-critical score was higher in females than in males (p = 0.048). Interactive-critical scores were associated with the area of residence, civil status and socioeconomic status, with the highest score in urban area of ≥ 100.000 inhabitants (p = 0.045), in widow patients (p = 0.023) and in patients with high socioeconomic status (p = 0.018). Significant differences were observed between the different education levels, for both the functional and the interactive-critical scores (p = 0.002 and p < 0.001, respectively), the highest score was observed in patients who completed a university degree. The level of vaccine literacy for functional and interactive-critical scales were medium. Area of residence, civil status and socioeconomic status represented determinants of vaccine literacy interactive-critical scale. Educational attainment also contributes to vaccine literacy functional scale. Insight into these factors is required to ensure an optimal vaccine literacy level in patients with autoimmune diseases. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-022-02713-y.

Beneficial effect of Mediterranean diet on disease activity and cardiovascular risk in systemic lupus erythematosus patients: a cross-sectional study.

OBJECTIVE: To analyse the influence of the Mediterranean diet (Med Diet) on SLE activity, damage accrual and cardiovascular disease risk markers. METHODS: A cross-sectional study was conducted on 280 patients with SLE [46.9 (12.85) years]. Med Diet adherence was assessed through a 14-item questionnaire on food consumption frequency and habits (total score from 0 to 14 points; higher score is greater adherence to the Med Diet). CRP, homocysteine, SLEDAI-2K (SLE disease activity), and SLICC/ACR and SDI (damage accrual) were measured. Obesity, diabetes mellitus, hypertension and blood lipids, among others, were considered cardiovascular disease risk factors. RESULTS: Greater adherence to the Med Diet was significantly associated with better anthropometric profiles, fewer cardiovascular disease risk factors, and lower disease activity and damage accrual scores (P ≤ 0.001 for SLEDAI and SDI). An inverse relationship between the Med Diet score and SLEDAI (P ≥ 0.001; ß = -0.380), SDI (P ≤ 0.001; ß = -0.740) and hsCRP (P = 0.039; ß = -0.055) was observed. The odds ratio for having active SLE (SLEDAI ≥5) or the presence of damage (SDI ≥1) was lower among patients whose Med Diet score was higher (P ≤ 0.001). Finally, greater consumption of Med Diet foods (olive oil, fruits, vegetables, fish, etc.) and abstaining from red meat and meat products, sugars and pastries was associated with less SLE clinical activity and damage. CONCLUSION: Greater adherence to the Med Diet seems to exert a beneficial effect on disease activity and cardiovascular risk in SLE patients. To confirm these findings, further longitudinal studies would be of interest.

Immune thrombocytopenia and COVID-19: Case report and review of literature.

Immune thrombocytopenia, also known as immune thrombocytopenic purpura (ITP), has been reported as an important complication related to COVID-19.We present a 49-year-old male patient with systemic lupus erythematosus with lupus nephritis, antiphospholipid syndrome and history of ITP who developed an ITP flare in the context of COVID-19. He had no bleeding manifestations and had a good response to prednisone treatment.We review the characteristics of the cases reported to date in the literature, with an analysis of 57 patients. Mean age was 56 years (±19.6 SD), and 50.9% were male. This was the first episode of ITP in most of the patients (86.05%), with SARS-CoV-2 acting as the initial trigger. We found that ITP flares may appear in both mild and severe COVID-19 cases. They also appeared at any time during the course of the disease, 48.2% of patients developed it during hospitalization, while it was diagnosed at admission in the rest of the cases. Platelet counts were significantly lower than other ITP series, with a median nadir platelet count of 8 × 109/L (IQR 2-17.75 × 109/L). These patients show a higher bleeding rate (61.4%) compared with other ITP series. They also show a better response to treatment, with good response to the first line therapies in 76.9% of them. The most common first-line treatment was intravenous immunoglobulin (IVIG), used alone or combined with corticosteroids in 40.4% and 32.7% of cases respectively, while 25% of patients received only corticosteroids.Our review suggests that COVID-19-related ITP can be seen even in previously healthy patients. Clinicians must be aware that ITP may appear both in mild and severe COVID-19, at any time during its course. Given that this kind of ITP seems to be associated with a higher bleeding risk, its diagnosis in a clinical scenario such as COVID-19, where anticoagulant therapy is frequently used, may be critical. Treatment with IVIG and/or corticoids is often effective.

Association Between FGF-23 Levels and Risk of Fracture in Women With Systemic Sclerosis.

INTRODUCTION/BACKGROUND: The purpose of this study was to evaluate the association between Fracture Risk Assessment Tool (FRAX) and serum fibroblast grow factor-23 (FGF-23) levels in SSc women patients compared with healthy controls. METHODOLOGY: This cross-sectional study was performed in San Cecilio Hospital, Granada (Spain) from November 2017 to May 2019. Sixty-two women with SSc and 62 age and sex matched healthy controls were included in this study. FGF-23 serum concentration was evaluated by indirect enzyme-linked immunosorbent assay. The FRAX scoring tool was applied using the on-line calculator (www.shef.ac.uk/FRAX). RESULTS: Even though there was no significant difference in FGF-23 levels between SSc women patients and healthy controls (78.2 ± 60.5 vs 80.3 ± 56.3 pg/mL, p = 0.662). FGF-23 levels were positively associated with FRAX index within the study group. CONCLUSIONS: This study shows that FGF-23 status is associated with FRAX index in women with SSc. FGF-23 could be a promising biomarker for detecting risk fracture in SSc women patients.

Sensorimotor tongue evaluation and rehabilitation in patients with sleep-disordered breathing: a novel approach.

STUDY OBJECTIVES: To evaluate tone, apraxia and stereognosis dysfunctions in patients with SDB compared with healthy controls, and to monitor the effectiveness of Airway Gym® as an easy-to-use myofunctional therapy (MT) modality in terms of the tongue's motor and sensory responses, comparing results before and after therapy. METHODS: This was a prospective, non-randomised pilot study of 25 patients with moderate to severe obstructive sleep apnoea-hypopnoea syndrome (OSAHS), 25 patients with primary snoring (PS) and 20 healthy controls. Qualitative and quantitative instruments-Iowa Oral Performance Instrument (IOPI), lingual apraxia and stereognosis tests were used to assess tongue sensorimotor function. RESULTS: 22 patients with PS, 21 with OSAHS and all 20 controls ended the therapy. In OSAHS, the Epworth Sleepiness Scale score decreased from 16 ± 7.3 to 12 ± 4.5 after therapy (p = 0.53). In PS and OSAHS groups, the IOPI scores increased significantly. These measures did not change significantly in the controls. Lingual apraxia testing showed that controls performed all the manoeuvres, whereas PS 5.6 ± 1.4 and OSAHS 4.5 ± 1.9 (p = 0.14). In the stereognosis test, the mean number of figures recognised was 2.6 ± 2.2 in OSAHS, 3.3±1.2 in PS and 5.7±0.9 in control group (p < 0.05). Patients with OSAHS recognised circles and ovals less often. CONCLUSION: Using the Airway Gym® app produced improvements in sensorimotor tongue function in patients with SDB, due to continuous stimulation of the brain based on proprioceptive training required to localise responses when doing the exercises.

Venous thrombosis and relapses in patients with Behçet's disease. Descriptive analysis from Spanish network of Behçet's disease (REGEB cohort).

OBJECTIVES: To describe the characteristics of patients with Behçet's disease (BD) who presented with venous thrombosis. In addition, we identified the factors associated with this venous involvement and those related with recurrent venous thrombosis. METHODS: Up to January 2015, 544 BD patients from 20 Spanish hospitals had been included in the REGEB (REGistro de la Enfermedad de Behçet as Spanish nomenclature). We selected those patients who presented venous thrombosis. Descriptive analysis was performed and factors related with venous thrombosis were identified. RESULTS: Overall, 99 (18.2%) BD patients had vascular thrombosis, 91 (16.7%) of them (16.7%) involving venous vessels and 18 (19.7%) suffered from venous thrombotic relapse. Lower limbs were the most common location of deep venous thrombosis present in up to 60% of patients. In 12 (13.2%) patients, venous thrombosis affected two vascular territories simultaneously and in 6 (6.6%) the venous and arterial involvement coincided in time. Overall, at the diagnosis of venous thrombosis, 97.6% of patients presented concomitantly other clinical symptoms attributable to BD. In logistic regression multivariate analysis factors associated to venous thrombosis were male sex (Odds ratio [OR] 4.3, 95% confidence interval [CI] 2.5-7.7), erythema nodosum (OR 2.4, 95%CI 1.4-4.1), fever (OR 2.0, 95%CI 1.1-3.8), and central nervous system (CNS) involvement (OR 2.5, 95%CI 1.3-4.8). Considering relapses, CNS involvement was an independent risk factor according logistic regression. However, Cox multivariate analysis did not confirm this finding. CONCLUSIONS: We identified factors related with venous involvement in patients included in the REGEB cohort.

Tocilizumab as an Adjuvant Therapy for Hemophagocytic Lymphohistiocytosis Associated With Visceral Leishmaniasis.

Leishmaniasis is important as a cause of hemophagocytic lymphohistiocytosis (HLH) and must be considered and excluded in patients with HLH because it can cause severe or even fatal complications. When HLH is present, there is a deficient downregulation of the immune response, leading to an uncontrolled inflammation. We report a case of visceral leishmaniasis-HLH where the therapy with tocilizumab, targeting interleukin 6, help to regulate the immune response for the infection of Leishmania.

Registry of the Spanish network of Behçet's disease: a descriptive analysis of 496 patients.

OBJECTIVES: To describe the clinical features of a large cohort of 496 Spanish patients with Behçet's disease (BD) and to analyse if patient's sex influenced the initial and cumulated prevalence of disease manifestations. METHODS: Retrospective and descriptive study of 496 patients recruited in sixteen centres on the frame of the Spanish Registry of Behçet Disease Project Group. Demographic and clinical data are presented in addition to treatments and their related adverse effects. Clinical features at disease onset and during follow-up were compared according to the sex of the patients. RESULTS: On the whole series, female to male ratio was 1.2:1.0. Mean age at disease onset was 28.7±12.6 years (range 17-73). Oral ulcers were the most frequent initial manifestation presented in 52.0% of patients. During follow-up, eye inflammatory disease was recorded in 45.1% of patients; thrombosis in 19.7% and central nervous system involvement in 13.5%. Men had higher prevalence of ocular involvement and venous thrombosis (52.5% vs. 39.2%, p=0.004 and 26.3% vs. 9.6%, p<0.001, respectively). CONCLUSIONS: Spanish patients with BD presented similar clinical characteristics as their counterpart in the same geographical area and other world regions. In addition, we confirmed that ocular and vascular involvements are more frequent in men than in women.

IL2/IL21 region polymorphism influences response to rituximab in systemic lupus erythematosus patients.

To determine whether the IL2/IL21 region, a general autoimmunity locus, contributes to the observed variation in response to rituximab in patients with systemic lupus erythematosus as well as to analyze its influence in a cohort including other autoimmune diseases. rs6822844 G/T polymorphism at the IL2-IL21 region was analyzed by TaqMan assay in 84 systemic lupus erythematosus (SLE) and 60 different systemic autoimmune diseases Spanish patients receiving rituximab. Six months after the first infusion patients were classified, according to the EULAR criteria, as good responders, partial responders and non-responders. A statistically significant difference was observed in GG genotype frequency between responder (total and partial response) (83.56%) and non-responder (45.45%) SLE patients (p=0.010, odds ratio (OR)=6.10 [1.28-29.06]). No association with the response was evident in the group of patients with autoimmune diseases other than lupus. Furthermore, when both groups of patients were pooled in a meta-analysis, a reduced statistical significance of the association was observed (p=0.024, OR=3.53 [1.06-11.64]). Our results show for a first time that IL2-IL21 region seems to play a role in the response to rituximab in SLE patients but not in other autoimmune diseases.

Off-label uses of anti-TNF therapy in three frequent disorders: Behçet's disease, sarcoidosis, and noninfectious uveitis.

Tumoral necrosis factor α plays a central role in both the inflammatory response and that of the immune system. Thus, its blockade with the so-called anti-TNF agents (infliximab, etanercept, adalimumab, certolizumab pegol, and golimumab) has turned into the most important tool in the management of a variety of disorders, such as rheumatoid arthritis, spondyloarthropatties, inflammatory bowel disease, and psoriasis. Nonetheless, theoretically, some other autoimmune disorders may benefit from these agents. Our aim is to review these off-label uses of anti-TNF blockers in three common conditions: Behçet's disease, sarcoidosis, and noninfectious uveitis. Due to the insufficient number of adequate clinical trials and consequently to their lower prevalence compared to other immune disorders, this review is mainly based on case reports and case series.

Adalimumab for the treatment of Behçet's disease: experience in 19 patients.

OBJECTIVE: To describe the experience of two tertiary Spanish centres (Hospital Clínico San Cecilio, Granada and Hospital Clínic, Barcelona) with the use of adalimumab for the treatment of severe clinical manifestations in patients with Behçet's disease (BD) in whom immunosuppressive therapy had failed. METHODS: Retrospective chart review from patients with BD treated with adalimumab in two specialized Spanish centres (Hospital Clínico San Cecilio, Granada and Hospital Clínic, Barcelona). RESULTS: From November 2006 to February 2011, 19 patients with BD were treated with adalimumab. The reason to initiate adalimumab was refractory disease in 17 (89.5%) patients and adverse events to CSA and infliximab in two (10.5%) patients, respectively. The main clinical manifestations leading to adalimumab administration were panuveitis in eight patients, severe bipolar aphthosis in eight, retinal vasculitis in three and severe folliculitis in three. Overall, adalimumab achieved clinical improvement in 17 of the 19 patients. Of note, ocular manifestations (panuveitis and retinal vasculitis) responded rapidly in all cases. In addition to clinical improvement, treatment with adalimumab was associated with reduction in the number and dose of standard immunosuppressive agents. Of interest, seven patients had received TNF-α inhibitors before adalimumab, five infliximab and the remaining two etanercept. Adalimumab was withdrawn in only one patient due to severe infusional reaction in the form of urticaria and angioedema. CONCLUSION: Adalimumab is a valid option for patients with BD and recalcitrant non-controlling manifestations with good safety profile.

Analysis of Class II human leucocyte antigens in Italian and Spanish systemic sclerosis.

OBJECTIVE: To determine the role of Class II HLAs in SSc patients from Italy and Spain and in SSc patients of Caucasian ancestry. METHODS: Nine hundred and forty-four SSc patients (Italy 392 patients; Spain 452 patients) and 1320 ethnically matched healthy controls (Italy 398 patients; Spain 922 patients) were genotyped up to the fourth digit by PCR with sequence-specific oligonucleotides for HLA-DRB1, DQA1 and DQB1 loci. Patients included 390 ACA-positive and 254 anti-topo I-positive subjects. Associations between SSc or SSc-specific antibodies and HLA alleles or HLA haplotypes were sought via the chi-square test after 10 000-fold permutation testing. A meta-analysis including this study cohort and other Caucasoids samples was also conducted. RESULTS: In both the cohorts, the strongest association was observed between the HLA-DRB1*1104 allele and SSc or anti-topo I antibodies. The HLA-DRB1*1104 -DQA1*0501 -DQB1*0301 haplotype was overrepresented in Italian [odds ratio (OR) = 2.069, 95% asymptotic CIs (CI(95)) 1.486, 2.881; P < 0.001] and in Spanish patients (OR = 6.707, CI(95) 3.974, 11.319; P < 0.001) as well as in anti-topo-positive patients: Italy (OR = 2.642, CI(95) 1.78, 3.924; P < 0.001) and Spain (OR = 20.625, CI(95) 11.536, 36.876; P < 0.001). In both the populations we also identified an additional risk allele (HLA-DQB1*03) and a protective allele (HLA-DQB1*0501) in anti-topo-positive patients. The meta-analysis showed different statistically significant associations, the most interesting being the differential association between HLA-DRB1*01 alleles and ACAs (OR = 1.724, CI(95) 1.482, 2.005; P < 0.001) or topo I antibodies (OR = 0.5, CI(95) 0.384, 0.651; P < 0.001). CONCLUSIONS: We describe multiple robust associations between SSc and HLA Class II antigens in Caucasoids that may help to understand the genetic architecture of SSc.

Bone mass and vitamin D in patients with systemic sclerosis from two Spanish regions.

OBJECTIVES: To study the bone mass in patients with scleroderma (SSc) from two different Spanish regions and to evaluate the prevalence of vitamin D deficiency and insufficiency in this population and its possible relation to bone mineral density (BMD). METHODS: Disease, bone mineral density related variables and vitamin D were collected from all patients. Statistical analysis was carried out using the SPSS 17 statistics software for Windows. A p<0.05 was considered significant. RESULTS: A Z-score <-1 was found in 21.9% of the control population and 43% of SSc patients. The prevalence of osteopenia/osteoporosis was 50% in the control population and 77% in SSc (p<0.0001). We did not find differences between the prevalence of low BMD in the south (79%) and in the north of Spain (76.3%); but patients from the north had lower levels of vitamin D (27.4±16.2 ng/dL vs. 20.7±11.0 ng/dl; p<0.031). Low levels of vitamin D (<30ng/ml) were found in 69 patients out of 90, ten of them with insufficiency (<10ng/ml). Eighty-four point six percent of the patients with low levels of vitamin D (<30ng/ml) had LBMD compared whith 66.7% of those with normal levels (p=0.073). CONCLUSIONS: The prevalence of osteoporosis/osteopenia in Spanish patient with SSc is very high. Although there are a high prevelence of vitamin D deficiency, we could not demonstrate a relationship of vitamin D deficiency with low mineral density.

Tongue infarction as first symptom of temporal arteritis.

Giant cell arteritis (GCA) is the most common systemic vasculitis affecting people over 50 years. This disease is a diagnostic challenge with a range of clinical symptoms and findings due to different affected vessels. Because of this, the initial diagnosis can be tricky, and some of the patients present at first time with a real unusual initial manifestation. One of these can be tongue necrosis, which is according to the literature in accordance with scalp necrosis, the rarest initial manifestation of GCA We describe a patient who presented with tongue necrosis as initial symptom of GCA. The belated diagnose resulted in subtotal necrosis of the mobile part of the tongue.

Altered AKT1 and MAPK1 gene expression on peripheral blood mononuclear cells and correlation with T-helper-transcription factors in systemic lupus erythematosus patients.

Kinases have been implicated in the immunopathological mechanisms of Systemic Lupus Erythematosus (SLE). v-akt murine-thymoma viral-oncogene-homolog 1 (AKT1) and mitogen-activated-protein-kinase 1 (MAPK1) gene expressions in peripheral mononuclear cells from thirteen SLE patients with inactive or mild disease were evaluated using quantitative real-time reverse-transcription polymerase-chain-reaction and analyzed whether there was any correlation with T-helper (Th) transcription factors (TF) gene expression, cytokines, and S100A8/S100A9-(Calprotectin). Age- and gender-matched thirteen healthy controls were examined. AKT1 and MAPK1 expressions were upregulated in SLE patients and correlated with Th17-(Retinoic acid-related orphan receptor (ROR)-C), T-regulatory-(Treg)-(Transforming Growth Factor Beta (TGFB)-2), and Th2-(interleukin (IL)-5)-related genes. MAPK1 expression correlated with Th1-(IL-12A, T-box TF-(T-bet)), Th2-(GATA binding protein-(GATA)-3), and IL-10 expressions. IL-10 expression was increased and correlated with plasma Tumor Necrosis Factor (TNF)-α and Th0-(IL-2), Th1-(IL-12A, T-bet), GATA3, Treg-(Forkhead/winged-helix transcription factor- (FOXP)-3), and IL-6 expressions. FOXP3 expression, FOXP3/RORC, and FOXP3/GATA3 expression ratios were increased. Plasma IL-1ß, IL-12(p70), Interferon-(IFN)-γ, and IL-6 cytokines were augmented. Plasma IL-1ß, IL-6, IL-2, IFN-γ, TNF-α, IL-10, and IL-13 correlated with C-reactive protein, respectively. Increased Calprotectin correlated with neutrophils. Conclusion, SLE patients presented a systemic immunoinflammatory activity, augmented AKT1 and MAPK1 expressions, proinflammatory cytokines, and Calprotectin, together with increased expression of Treg-related genes, suggesting a regulatory feedback opposing the inflammatory activity.