Assessment of microvascular involvement in lupus nephritis patients by retinal OCT-angiography and kidney biopsies.

OBJECTIVES: Ocular and renal microvascular damage in lupus nephritis (LN) share similar physiopathological pathways that have investigated using traditional fundus examination and high-resolution colour electroretinography. Optical coherence tomography angiography (OCTA) is a recent, non-invasive technique for imaging the microvasculature of retina and choroid. Aim of the study was to investigate through OCTA analysis the relationship between retinal microvascular alterations and renal functional and histologic features. METHODS: Systemic lupus erythematosus (SLE) patients with LN, SLE without renal involvement and healthy controls were recruited and accomplished an ophthalmological evaluation, including OCTA. SLE-LN patients underwent a rheumatological evaluation, including disease-related clinical and laboratory features collection and kidney biopsy examination. RESULTS: This cross-sectional study enrolled forty-six eyes of 23 LN patients, thirty-two eyes of 16 SLE patients and forty-two eyes of 21 controls. Thirteen SLE-LN patients (56.5%) displayed lupus retinopathy, 10 at moderate (77%) and 3 at severe stage (23%) by fundus oculi examination. Analysis of OCTA data showed with high/moderate accuracy a reduction of retinal capillary vessel density in both SLE and SLE-LN patients compared to controls in superficial and deep plexi. A reduction in fovea thickness and an increase in foveal avascular zone were also detected. OCTA data of LN patients correlated with LN duration, disease activity, kidney function and the presence of LN-vascular lesions at kidney biopsy. CONCLUSIONS: Our results suggest the role of OCTA in early detection of systemic vascular involvement in SLE-LN patients and related kidney functional-histological impairment.

How Has Molecular Biology Enhanced Our Undertaking of axSpA and Its Management.

PURPOSE: This review aims at investigating pathophysiological mechanisms in spondyloarthritis (SpA). Analysis of genetic factors, immunological pathways, and abnormalities of bone metabolism lay the foundations for a better understanding of development of the axial clinical manifestations in patients, allowing physician to choose the most appropriate therapeutic strategy in a more targeted manner. RECENT FINDINGS: In addition to the contribution of MHC system, findings emerged about the role of non-HLA genes (as ERAP1 and 2, whose inhibition could represent a new therapeutic approach) and of epigenetic mechanisms that regulate the expression of genes involved in SpA pathogenesis. Increasing evidence of bone metabolism abnormalities secondary to the activation of immunological pathways suggests the development of various bone anomalies that are present in axSpA patients. SpA are a group of inflammatory diseases with a multifactorial origin, whose pathogenesis is linked to the genetic predisposition, the action of environmental risk factors, and the activation of immune response. It is now well known how bone metabolism leads to long-term structural damage via increased bone turnover, bone loss and osteoporosis, osteitis, erosions, osteosclerosis, and osteoproliferation. These effects can exist in the same patient over time or even simultaneously. Evidence suggests a cross relationship among innate immunity, autoimmunity, and bone remodeling in SpA, making treatment approach a challenge for rheumatologists. Specifically, treatment targets are consistently increasing as new drugs are upcoming. Both biological and targeted synthetic drugs are promising in terms of their efficacy and safety profile in patients affected by SpA.

Rheumatologist's Perspective on Non-Infectious Uveitis: Patterns from Tertiary Referral Rheumatologic Clinics in Italy.

Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behçet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27+ patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27- patients. On the contrary, HLA-B51+ patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51- patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies.

Adherence of Italian rheumatologists to the EULAR recommendations and outcomes in early rheumatoid arthritis patients after starting conventional DMARDs: Methotrexate in Italian patients wiTh Rheumatoid Arthritis (the MITRA study). A cohort study of the Italian Society for Rheumatology.

OBJECTIVES: The aim of this study was to assess the real-life adherence of Italian rheumatologist to the 2013 EULAR recommendations and treatment outcome in rheumatoid arthritis (RA) patients who started a conventional synthetic disease-modifying anti-rheumatic drug (csDMARD). METHODS: The MITRA study is an Italian multicentre observational cohort focused on treatment naïve RA patients with early diagnosis recruited in an 18-month period starting from 2015. The data related to treatment with csDMARDs during the following 12 months follow-up were presented in this paper. RESULTS: Two-hundred and fifty-nine RA patients from MITRA cohort who had a follow-up visit and started a csDMARD were included in the prospective analysis. Methotrexate was started as first conventional DMARD in 224 (86.4%) patients. During the first year after starting conventional DMARDs, 175 (67.6%) RA patients reached the pre-specified target, which was DAS28 remission (<2.6) for 112 (43.2%) patients and LDA (<3.2) for 63 (24.3%) patients. Factors that negatively impacted the target achievement were fibromyalgia (HR: 0.2 [0.05-0.81]), HAQ-DI (HR: 0.72 [0.56-0.93]) and ESR (HR: 0.99 [0.99-1]). Globally, 33 (12.7%) patients started a biologic DMARD, while 61 out of 84 (72.6%) patients who had never reached the target remained on conventional DMARD. One-hundred and ninety-three adverse events (AEs) were recorded, the majority classified as mild (91 cases, 51%). CONCLUSIONS: A high proportion of RA patients achieved the target during the first-year follow-up. However, a considerable portion of RA patients did not start a biological drug although the target was never reached. AEs remain frequent with conventional DMARDs, but the majority were mild.

Baseline characteristics of systemic lupus erythematosus patients included in the Lupus Italian Registry of the Italian Society for Rheumatology.

OBJECTIVE: To report baseline data of SLE patients enrolled in the Lupus Italian Registry (LIRE). METHODS: Patients affected by SLE aged ≥ 16 years were consecutively recruited in a multicenter prospective study comparing two cohorts: patients starting biologic immunosuppressants (BC) and patients starting non-biologic immunosuppresants (NBC). RESULTS: 308 patients were enrolled, 179 in NBC and 129 in BC. Mean age at disease onset and at diagnosis was significantly higher in NBC (p = 0.023, p = 0.045, respectively). Disease duration was longer in BC (p = 0.022). Patients in BC presented arthritis more frequently (p = 0.024), those in NBC nephropathy (p = 0.03). Quality of life was worse in BC (p = 0.031). Anti-dsDNA, low C3, were significantly more frequent in BC (p < 0.001, p = 0.009, respectively). Mycophenolate, methotrexate and azathioprine were the drugs more frequently prescribed in NBC, Belimumab and Rituximab in BC. CONCLUSION: The predominant organ involvement was different in the two cohorts: kidney involvement predominated in NBC, joint involvement in BC. Despite the younger age at disease onset, patients of the BC had a longer disease duration and more frequently had taken a cumulative prednisone dosage greater than 10 g. Even the pattern of clinical manifestations inducing to prescribe biological rather than conventional immunosuppressants was quite different.Keywords: Autoantibody(ies), autoimmune disease, belimumab, cohort studies, glucocorticoids, immunosuppressants, rituximab, systemic lupus erythematosus.

Methotrexate in Italian patients wiTh Rheumatoid Arthritis (MITRA study): an observational study about the use of methotrexate in early RA patients and the adherence to the EULAR 2013 recommendations. A project of the Italian Society for Rheumatology.

OBJECTIVES: To assess the delay between the disease onset and the beginning of methotrexate (MTX) treatment in RA patients and to evaluate the Italian rheumatologists' adherence to the EULAR 2013 recommendations. METHODS: MITRA is an Italian multicentre observational study carried out on DMARD-naïve RA patients recruited in an 18-month period starting from 2015. The data related to the patients' characteristics at baseline will be presented. RESULTS: 332 patients from 13 Italian centres were recruited: the median delay between the onset of symptoms and the beginning of MTX was 197 days (102-431); in 20% of patients a treatment with DMARDs was started within the first 90 days from the onset of symptoms. The clinical target selected was DAS28 remission in 64.2% of cases and low disease activity in 35.8%. Among patients in DAS28 high disease activity, 92.6% received a control visit which was rescheduled within the first 3 months, similarly to those in DAS28 moderate disease activity (91.6%). A DMARD monotherapy was prescribed in 319 patients, while a combined therapy of DMARDs was preferred in 13 cases; 282 patients were treated with MTX. Glucocorticoids were prescribed in 229 patients: the median dosage was of 5 mg (IQR 5-7.5) of prednisone equivalent/day. CONCLUSIONS: Diagnostic delay in RA patients continues to be longer than expected. The choice of low disease activity as a target is still very frequent and tight control does not seem to be based on disease activity. This paper offers a realistic and detailed picture of the clinical practice among Italian rheumatologists.

The burden of depressive disorders in musculoskeletal diseases: is there an association between mood and inflammation?

IMPORTANCE: Evidence emerged concerning how inflammatory arthritis and mood disorders can often occur in the same patient and show a similar clinical pattern. An overview of the rheumatological and psychiatric aspects of these diseases can certainly be useful for the improvement of patients' clinical and therapeutic management. OBJECTIVE: The aim of this narrative review was to summarize existing literature about common pathogenetic and clinical aspects as a means of improving management and therapeutic approach in patients affected by rheumatoid arthritis, psoriatic arthritis and spondyloarthritis. Outcomes such as disease activity indexes and patient reported outcomes (PROs) were considered. FINDINGS: Common pathogenetic pathways emerged between inflammatory arthritis and mood disorders. Pro-inflammatory mechanisms, such as TNFα, IL-6, IL-17 and oxidative stress factors as well as neurotransmitter alterations at the level of CNS and blood-brain barrier (BBB) cells are involved. The activation of these common pathogenetic pathways is, also, affected by the same triggers, such as smoking, stress, lifestyle, and evidence has emerged concerning the possibility of the clinical efficacy of using the same therapeutic approaches. CONCLUSIONS: The main causes of the variability in clinical studies outcomes are the rheumatological diseases considered, the prevalence of depression in the general population and in patients with rheumatological diseases and the type of depressive symptom examined. Patients affected by inflammatory arthritis can present symptoms and signs in common with mood disorders, leading to possible clinical overlap. There are still few studies analyzing this concept: they are extremely heterogeneous, both in the characteristics of the population taken into consideration and in the methods used for the definition of depressive disorder, but the suggestions of the data obtained so far are promising and deserve to be pursued.

Demographic and clinical differences between ankylosing spondylitis and non-radiographic axial spondyloarthritis: results from a multicentre retrospective study in the Lazio region of Italy.

OBJECTIVES: Axial spondyloarthritides (axSpA) are a group of disorders that share similar pathogenetic mechanisms and clinical picture. The aim of this retrospective multicentric study was to evaluate demographic and clinical differences between ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA) patients. METHODS: Patients from 7 rheumatological centres in the Lazio region of Italy were included from January 1st, 2010 to April 1st, 2018, if they had undergone pelvic and/or spine radiographs or magnetic resonance imaging (MRI). Images were evaluated by one experienced radiologist in each centre who already had the clinical suspicion of axSpA. Clinical and therapeutic data were collected at the last observation visit. Categorical variables were presented with percentages and analysed by Chi squared test. Continuous variables were expressed as mean ± standard deviation and compared using the parametric unpaired t-test or the non-parametric Mann-Whitney U-test, when appropriate. p-values <0.05 were considered significant. RESULTS: 210 axSpA patients were included: 65.2% with AS and 34.7% with nr-axSpA. When comparing the two groups, AS patients had longer disease duration, were older, were more frequently males, had a greater diagnostic delay and a higher body mass index than the nr-axSpA patients (p<0.0001, p<0.0001, p=0.003 p=0.007, and p=0.04, respectively). The peripheral joints of the nr-axSpA patients were more frequently involved, had higher frequency of inflammatory bowel disease, higher C-reactive protein levels and lower frequency of HLA-B27 positivity (p=0.005, p=0.007, p=0.01, and p=0.01, respectively). TNF inhibitors were used in 87.8% patients with AS and 78.3% with nr-axSpA (p=0.04). More fat metaplasia was observed on MRI in the nr-axSpA group than in the AS group at sacroiliac joints (p=0.003), and more backfills were detected in the AS group on spine-MRI (p=0.003). Spine-bone marrow oedema was more prevalent in AS than in nr-axSpA (p=0.04), and more sclerosis and backfill were found in AS (p=0.003 and p=0.01, respectively). CONCLUSIONS: In clinical practice, distinctive features in AS and nr-axSpA patients emerged. Imaging is crucial in guiding the choice of treatment in order to control disease activity and inflammation.

Complement, infection, and autoimmunity.

PURPOSE OF REVIEW: Complement system dysfunction in terms of upregulation, downregulation, or dysregulation can create an imbalance of both host defense and inflammatory response leading to autoimmunity. In this review, we aimed at describing the role of complement system in host defense to inflection and in autoimmunity starting from the evidence from primary and secondary complement system deficiencies. RECENT FINDINGS: Complement system has a determinant role in defense against infections: deficiencies of complement components are associated with increased susceptibility to infections. Primary complement system deficiencies are rare disorders that predispose to both infections and autoimmune diseases. Secondary complement system deficiencies are the result of the complement system activation with consumption. Complement system role in enhancing risk of infective diseases in secondary deficiencies has been demonstrated in patients affected by systemic autoimmune disorders, mainly systemic lupus erythematosus and vasculitis. SUMMARY: The relationship between the complement system and autoimmunity appears paradoxical as both the deficiency and the activation contribute to inducing autoimmune diseases. In these conditions, the presence of complement deposition in affected tissues, decreased levels of complement proteins, and high levels of complement activation fragments in the blood and vessels have been documented.

Use of synthetic and biological DMARDs in patients with enteropathic spondyloarthritis: a combined gastro-rheumatological approach.

OBJECTIVES: The aim of this 2-year prospective study was to assess the diagnostic and therapeutic effect of a combined gastro-rheumatological approach in enteropathic spondyloarthritis (eSpA) patients. METHODS: Inflammatory bowel disease (IBD) patients with joint pain were referred by IBD-dedicated gastroenterologists to a dedicated rheumatologist. At baseline and at 3, 6, 12, 24 months, the following parameters were recorded: clinical and biochemical variables, SpA and IBD activity scores, treatment (conventional synthetic; csDMARDs, biologics; bDMARDs). Associations between treatment and patient characteristics were evaluated by logistic regression (AOR [95% CI]). RESULTS: Overall, 229 IBD patients were referred to rheumatologists. eSpA was diagnosed in 147 (64.2%) patients: 96 (65.3%) showing peripheral and 51 (34.7%) axial involvement. IBD included Crohn's disease (CD) in 141 (61.6%) and ulcerative colitis (UC) in 88 (38.4%). bDMARD treatment increased over the follow-up (baseline-24 months: 32.7-60%; AOR 3.45 [1.93-6.2], p<0.001). bDMARD use was less frequent in elderly patients (AOR 0.73 [0.56-0.96], p=0.023), in UC (AOR 0.43 [0.2-0.94], p=0.034) and in patients with peripheral involvement (AOR 0.53 [0.3-1.04], p=0.067). csDMARD use was increased in patients with peripheral involvement (AOR 4.65 [2.09-10.33], p<0.001) and in UC (AOR 2.30 [1.13-4.67], p=0.021). CRP, ESR, ASDAS-ESR levels and BASFI significantly decreased over the follow-up, whereas the pMayo score, BASDAI and HAQ-S were unchanged. CONCLUSIONS: In this prospective study in eSpA patients, a multidisciplinary approach was shown to optimise the therapeutic management and outcome (e.g. disease activity scores). bDMARD use paralleled an improvement in disease activity scores and confirmed a good safety profile.

Evidence for the Detection of Subclinical Retinal Involvement in Systemic Lupus Erythematosus and Sjögren Syndrome: A Potential Association with Therapies.

BACKGROUND: Retinal involvement in systemic lupus erythematosus (SLE) and Sjögren syndrome (SS) may be subclinical and thus underdiagnosed. OBJECTIVES: We aimed at evaluating morphological and functional visual abnormalities in a cohort of SLE and SS patients in the absence of an overt clinical visual impairment. We also investigated potential associations between retinal disorders and disease activity, organ involvement, and treatment with steroid and/or hydroxychloroquine. METHODS: The study comprised 42 SLE and 36 primary SS patients and 76 healthy controls (HC). Ophthalmological examination, standard automated perimetry, spectral-domain optical coherence tomography, and fundus perimetry were performed. RESULTS: Retinal thickness of the posterior pole was not different between SLE and HC groups, but it was reduced in the SS group compared with both the HC and the SLE group. In SLE and SS patients, mean defect and pattern standard deviation by standard automated perimetry were higher than in HC. Visual field index values were lower in both SLE and SS patients than in HC. SLE patients with nephritis displayed increased mean defect and pattern standard deviation and reduced visual field index values compared to patients without nephritis. In SLE and SS patients, fundus perimetry differential sensitivity was reduced, and mean defect values were higher than in HC. Disturbances in fundus perimetry in the SLE group were more prevalent in steroid-naïve patients and in SS patients who received a cumulative hydroxychloroquine dose > 1,000 g. CONCLUSIONS: Functional eye impairment was demonstrated in SLE patients, possibly associated with kidney involvement. In SLE, corticosteroids might exert a protective role. Morphological alterations and functional impairment were detected in SS patients, which may be linked to hydroxychloroquine toxicity.

Effects of Abatacept on T-Lymphocyte Sub-populations and Immunoglobulins in Patients Affected by Rheumatoid Arthritis.

BACKGROUND: Abatacept acts as a co-stimulation modulator preventing activation of T cells. Although it is approved for the treatment of rheumatoid arthritis (RA), its effects on adaptive immune response have not been fully elucidated. OBJECTIVES: To observe, in a cohort study, based on a clinical practice setting, the variation of peripheral blood T cells, immunoglobulin levels, and autoantibodies in the serum of RA patients during abatacept therapy. METHODS: Our study comprised 48 RA patients treated with abatacept. All clinical data were collected at baseline and after 3 months of treatment. Clinical and laboratory tests included erythrocyte sedimentation rate, C-reactive protein, 28-joint disease activity score, RF, anti-citrullinated protein antibody, total immunoglobulins, immunoglobulin A (IgA), immunoglobulin G (IgG), immunoglobulin M (IgM), and lymphocyte sub-population. RESULTS: Total immunoglobulin serum levels significantly decreased after 3 months of treatment and correlated positively with disease activity both at baseline and after 3 months of abatacept treatment. A reduction of serum IgM, IgG, IgA and RF was also demonstrated. The absolute number and percentage of cytotoxic (CD8+) T cells significantly decreased after 3 months of abatacept treatment, in particular the percentage of cytotoxic (CD8+) T cells significantly decreased only in patients responding to the treatment. CONCLUSIONS: Our results highlight a different role of abatacept in the modulation of the adaptive immune response in RA by the reduction of polyclonal B-cell activation and cytotoxic T cells.

Factors Predicting 2 Years of Remission and Low Disease Activity in Rheumatoid Arthritis Patients Treated with TNF-inhibitors.

BACKGROUND: The goals of treatment for rheumatoid arthritis (RA) are remission and low disease activity (LDA). However, many patients do not reach or maintain these targets with regard to disease control. OBJECTIVES: To identify predictive factors of remission/LDA in a cohort of RA patients who started treatment with first line tumor necrosis factor-inhibitors (TNF-i). METHODS: We included 308 RA patients treated with first line TNF-i for 2 years to evaluate remission/LDA based on the 28-joint disease activity score (DAS28). Predictive factors considered for achievement of remission/LDA were: gender, age at the time of TNF-i treatment, early arthritis, baseline C-reactive protein (CRP) and erythrocyte sedimentation rate levels, RF/anti-citrullinated protein antibody positivity, good/moderate European League Against Rheumatism response at 6 months, co-morbidities, and concomitant disease modifying antirheumatic drugs (DMARDs). Intention to treat, receiver operating characteristic curve, and univariate and multivariate analyses by logistic regression were performed. RESULTS: Positive predictors of remission/LDA in both the univariate and the multivariate analyses were: male gender, age at the time of TNF-i treatment ≤ 54 years, negative baseline CRP, and concomitant DMARDs. The presence of any co-morbidity resulted to be a negative predictor of remission/LDA in both the univariate and the multivariate analyses. CONCLUSIONS: Demographic and clinical features were identified as reliable predictors of both the achievement and the maintenance of treatment targets in a cohort of RA patients treated for 2 years with first line TNF-i.

Systemic Sclerosis: Exploring the Potential Interplay Between Thyroid Disorders and Pregnancy Outcome in an Italian Cohort.

BACKGROUND: Evidence has shown that pregnancy failure (PF) in women with systemic sclerosis (SSc) consists mainly of preterm delivery (PD) and intrauterine growth restriction (IUGR). Thyroid dysfunction (TD) and Hashimoto's thyroiditis (HT) represent a common feature of SSc. Since TD has been associated with PF, its presence in SSc women may potentially affect pregnancy outcome. OBJECTIVES: To analyze the interplay between TD and PF in a cohort of SSc women. METHODS: SSc women (n=77) and age-matched controls from the general obstetric population (n=50) were included. Clinical/biochemical/instrumental data exploring TD and the visceral involvement were collected in the context of a clinical practice setting. Pregnancy outcome was assessed by registering the history of primary infertility, recurrent spontaneous abortion, PD (≤ 37 gestational week), IUGR, and intrauterine fetal death. RESULTS: A higher prevalence of PD/IUGR was recorded in the SSc cohort than the controls (P = 0.04). SSc women with PF showed a higher prevalence of diffuse SSc than women without PF (P = 0.03). Scl-70 positive SSc women had a higher prevalence of PF than women with anti-centromere positivity (P = 0.01). A higher prevalence of HT was recorded in SSc women with PF than in patients without (P = 0.04). CONCLUSIONS: Our findings support the evidence that women with SSc can have successful pregnancies despite a higher prevalence of PD/IUGR. Diffuse SSc and Scl-70 positivity may predispose SSc women to PF. Routine thyroid workup may be included in the multi-specialist monitoring of SSc women for the early detection of thyroid dysfunctions.

Evidence of IL-17 producing innate lymphoid cells in peripheral blood from patients with enteropathic spondyloarthritis.

OBJECTIVES: Both the innate and the adaptive immune responses contribute to the onset of chronic inflammation in spondyloarthritis (SpA). The association between SpA and inflammatory bowel disease (IBD, enteropathic SpA-ESpA) has been largely established and suggests a shared pathophysiology. There is evidence that innate lymphoid cells (ILC) are involved in the pathogenesis of both SpA and IBD while no evidence has been reported to date on ESpA. We aimed to analyse for the first time the frequency and cytokine expression of ILC in peripheral blood from ESpA patients compared with both IBD and healthy subjects. Correlations between immunophenotyping and disease activity were also explored. METHODS: ESpA patients (n=20) were prospectively enrolled. Healthy controls (HC, n=10) and IBD patients (n=10) served as control groups. Peripheral blood Interferon (IFN)-γ and interleukin (IL)-17 expressing T and non-T cells as well as ILC subsets (ILC-1: IFN- γ +; ILC-3: IL-17+; natural killer-NK) were characterised by flowcytometry. Correlations between IL-17+ cells and SpA disease activity were analysed. RESULTS: ESpA patients showed higher levels of ROR-γ expressing non T-cells with the respect to the controls. IL-17 producing non-T cells were higher than the HC and positively correlated with IFN-γ expressing cells levels as well as with SpA disease activity. ESpA showed higher levels of ILC-1 and ILC-3 than both IBD and HC. IFN-γ expressing NK cells were higher in ESpA than HC. CONCLUSIONS: Our preliminary findings indicate that peripheral blood of ESpA patients is enriched for IL-17 expressing ILC which distinguishes the blood compartment from both IBD and HC. The increased IL-17 production by ILC indicates a novel role for ILC in ESpA.