Low-risk delisting strategy in highly sensitized patients without donor offers included in exchange donation programs. One single-center experience.

Donor exchange programs were designed to allocate organs for highly sensitized (HS) patients. The allocation algorithm differs slightly among countries and includes different strategies to improve access to transplants in HS patients. However, many HS patients with a calculated panel reactive of antibodies (cPRA) of 100 % remain on the waiting list for a long time. Some allocation algorithms assume immunological risk, including Imlifidase treatment, to increase the chance of transplantation in very HS patients. Here, we describe our unicenter experience of low-risk delisting strategy in 15 HS patients included in the Spanish donor exchange program without donor offers. After delisting, 7 out of 15 HS patients reduced the cPRA below 99.95 % and impacted the reduction of time on the waiting list (p = 0.01), where 5 out of 7 achieved transplantation. Within those HS that remained above 99.95 %, 1 out of 8 was transplanted. All the HS were transplanted with delisted DSA, and only one with DSA level rebounded early after transplantation. All HS transplanted after delisting maintain graft function. The transplant immunology laboratories are challenged to search intermediate risk assessment methods for delisting high HS patients.

Plasma Phosphorylated Tau 231 Increases at One-Year Intervals in Cognitively Unimpaired Subjects.

Background: Plasma biomarkers of Alzheimer's disease (AD) constitute a non-invasive tool for diagnosing and classifying subjects. They change even in preclinical stages, but it is necessary to understand their properties so they can be helpful in a clinical context. Objective: With this work we want to study the evolution of p-tau231 plasma levels in the preclinical stages of AD and its relationship with both cognitive and imaging parameters. Methods: We evaluated plasma phosphorylated (p)-tau231 levels in 146 cognitively unimpaired subjects in sequential visits. We performed a Linear Mixed-effects Model to analyze their rate of change. We also correlated their baseline levels with cognitive tests and structural and functional image values. ATN status was defined based on cerebrospinal fluid biomarkers. Results: Plasma p-tau231 showed a significant rate of change over time. It correlated negatively with memory tests only in amyloid-positive subjects. No significant correlations were found with any imaging measures. Conclusions: Increases in plasma p-tau231 can be detected at one-year intervals in cognitively healthy subjects. It could constitute a sensitive marker for detecting early signs of neuronal network impairment by amyloid.

Influence of Physiological Variables and Comorbidities on Plasma Aß40, Aß42, and p-tau181 Levels in Cognitively Unimpaired Individuals.

Plasma biomarkers for Alzheimer's disease (AD) are a promising tool that may help in early diagnosis. However, their levels may be influenced by physiological parameters and comorbidities that should be considered before they can be used at the population level. For this purpose, we assessed the influences of different comorbidities on AD plasma markers in 208 cognitively unimpaired subjects. We analyzed both plasma and cerebrospinal fluid levels of Aß40, Aß42, and p-tau181 using the fully automated Lumipulse platform. The relationships between the different plasma markers and physiological variables were studied using linear regression models. The mean differences in plasma markers according to comorbidity groups were also studied. The glomerular filtration rate showed an influence on plasma Aß40 and Aß42 levels but not on the Aß42/Aß40 ratio. The amyloid ratio was significantly lower in diabetic and hypertensive subjects, and the mean p-tau181 levels were higher in hypertensive subjects. The glomerular filtration rate may have an inverse relationship on plasma Aß40 and Aß42 levels but not on the amyloid ratio, suggesting that the latter is a more stable marker to use in the general population. Cardiovascular risk factors might have a long-term effect on the amyloid ratio and plasma levels of p-tau181.

ANCA detection with solid phase chemiluminescence assay: diagnostic and severity association in vasculitis.

ANCA-associated vasculitis (AAV) comprises a group of necrotizing vasculitis that mainly affects small- and medium-sized vessels. Serum anti-neutrophil cytoplasmic antibodies (ANCA), mainly anti-myeloperoxidase (anti-MPO) and anti-proteinase 3 (anti-PR3), levels may correlate to severity, prognosis, and recurrence of the disease. A retrospective analysis of 101 patients with MPO-positive and 54 PR3-positive vasculitis was performed, using laboratory established cut-off value, measured by chemiluminescence. Furthermore, data of renal disease and pulmonary involvement were collected at vasculitis diagnosis, as well as the progress, requiring dialysis, transplant, or mortality. For anti-MPO antibodies with a diagnosis of vasculitis (n = 77), an area under the curve (AUC) was calculated (AUC = 0.8084), and a cut-off point of 41.5 IU/ml was determined. There were significant differences in anti-MPO levels between patients with renal or pulmonary dysfunction (n = 65) versus those without them (n = 36) (p = 0.0003), and a cut-off threshold of 60 IU/ml was established. For anti-PR3 antibodies with a diagnosis of vasculitis (n = 44), an area under the curve (AUC) was calculated (AUC = 0.7318), and a cut-off point of 20.5 IU/ml was determined. Significant differences in anti-PR3 levels were observed between those patients with renal or pulmonary dysfunction (n = 30) and those without them (n = 24) (p = 0.0048), and a cut-off threshold of 41.5 IU/ml was established. No significant differences between those patients who had a worse disease progression and those who did not were found for anti-MPO and anti-PR3. Anti-MPO and anti-PR3 levels at the moment of vasculitis diagnosis are related with disease severity but not with disease outcome or vasculitis recurrence.

Total error in lymphocyte subpopulations by flow cytometry-based in state of the art using Spanish EQAS data.

OBJECTIVES: Flow cytometry analyses of lymphocyte subpopulations (T, B, NK) are crucial for enhancing clinical algorithms and research workflows. Estimating the total error (TE) values for the percentage and absolute number of lymphocyte subpopulations using the state-of-the-art (SOTA) approach with real data from an external proficiency testing (EPT) scheme was performed. A comparison with previously published Biological Variability (BV)-based specifications was carried out. METHODS: A total of 44,998 results from 86 laboratories over 10 years were analysed and divided into two five-year periods (2012-2016) and (2017-2021). Data come from the IC-1 Lymphocytes scheme of the Spanish External Quality Assurance System (EQAS) GECLID Program. This quantitative scheme includes percentages and absolute numbers of CD3+, CD3+CD4+, CD3+CD8+, CD19+, and CD3-CD56+CD16+ NK cells. The percentage of TE was calculated as: |reported value - robust mean|*100/robust mean for each laboratory and parameter. The cut-off for TE is set at 80 % best results of the laboratories. RESULTS: A significant reduction in the SOTA-based TE for all lymphocyte subpopulations in 2017-2021 was observed compared to 2012-2016. The SOTA-based TE fulfils the minimum BV-based TE for percentages of lymphocyte subpopulations. The parameter with the best analytical performance calculated with SOTA (2017-2021 period)-based TE was the percentage of CD3+ (TE=3.65 %). CONCLUSIONS: The values of SOTA-based specifications from external quality assurance program data are consistent and can be used to develop technical specifications. The technological improvement, quality commitment, standardization, and training, reduce TE. An update of TE every five years is therefore recommended. TE assessment in lymphocyte subsets is a helpful and reliable tool to improve laboratory performance and data-based decision-making trust.

Prevalence and sociodemographic correlates of antinuclear antibody testing by indirect immunofluorescence or solid-phase assays in a Spanish population: the Camargo Cohort.

Autoantibodies are the hallmark of autoimmunity, and specifically, antinuclear antibodies (ANA) are one of the most relevant antibodies present in systemic autoimmune diseases (AID). In the present study, we evaluate the relationship between ANA and sociodemographic and biobehavioral factors in a population with a low pre-test probability for systemic AID. ANA were determined in serum samples at baseline visit from 2997 participants from the Camargo Cohort using indirect immunofluorescence assay, and two solid phase assays (SPA), addressable laser bead immunoassay, and fluorescence enzyme immunoassay. Sociodemographic and biobehavioral features of the subjects were obtained at baseline visit using a structured questionnaire. The prevalence of ANA positive results was significantly higher when indirect immunofluorescence assay was used as screening method in comparison with SPAs, being higher in females, older subjects, and those with higher C-reactive protein levels. Considering biobehavioral features, the prevalence was higher in those individuals with a sedentary lifestyle, and in ex- and non-alcohol users. Moreover, considering the relevance of the antibody load using ANA Screen, the prevalence of the antibody load also increased with age, especially in females. In conclusion, the prevalence of ANA varies depending on sociodemographic and biobehavioral features of the subjects, which could be relevant specifically in a population with a low pre-test probability for systemic AIDs.

Age-related hearing loss is not linked to cerebrospinal fluid levels of ß-amyloid or p-tau181.

INTRODUCTION: As Hearing loss and dementia affect people with the same profile, several epidemiological studies have evaluated their relationship. However, the link between age-related hearing loss and Alzheimer's disease is still unclear. METHODS: We selected subjects with no history of exposure to loud noises, blasts, head trauma with hearing loss, or sudden sensorineural hearing loss from a cohort intended to study preclinical phases of Alzheimer's disease. Participants are volunteers over 55 years without cognitive impairment. We correlated the results of an objective auditory evaluation with brain amyloid and p-tau181 levels and with the outcomes of a comprehensive neuropsychological assessment. RESULTS: Fifty-five subjects at different stages of the Alzheimer's disease continuum were evaluated. There were no statistically significant correlations between amyloid-ß and p-tau levels and any of the objective auditory measures. A weak but significant correlation was found between amyloid-ß values and the Hearing Handicap Inventory for the Elderly. The neuropsychological domains more correlated to hearing loss were executive function and processing speed. DISCUSSION: Age-related hearing loss is not linked to any pathological markers of Alzheimer's disease nor to neuropsychological domains typically affected in this disease. The Hearing Handicap Inventory for the Elderly has an important component of subjectivity and further studies are needed to explore its relationship with amyloid-ß levels.

Accuracy of plasma Aß40, Aß42, and p-tau181 to detect CSF Alzheimer's pathological changes in cognitively unimpaired subjects using the Lumipulse automated platform.

BACKGROUND: The arrival of new disease-modifying treatments for Alzheimer's disease (AD) requires the identification of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma Aß40, Aß42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. METHODS: Both plasma and CSF Aß40, Aß42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A - / +), AD status (considering AD + subjects to those A + plus Tau +), and ATN group defined by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and different combinations of plasma markers as predictors. RESULTS: Aß42, amyloid ratio, p-tau181, and p-tau181/Aß42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A + / - , AD + / - , and ATN groups. Amyloid ratio predicts amyloid and AD pathology in CSF with an AUC of 0.89. CONCLUSIONS: Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer's pathology in cognitively unimpaired subjects.

DQA1 Eplet Mismatch Load As an Independent Risk Factor of CLAD After Lung Transplantation.

Lung transplantation remains the treatment of choice for end-stage lung diseases, and recipient selection is currently based on clinical urgency, ABO compatibility, and donor size. The risk of allosensitization is classically based on HLA mismatch, but eplet mismatch load is increasingly seen to be important in long-term outcomes in solid organ transplantation. Chronic lung allograft dysfunction (CLAD) is relatively common and relevant, affecting almost 50% of patients 5 y after transplantation and being the first cause of death from the first year after transplantation. The overall class-II eplet mismatch load has been associated with CLAD development. Methods: Based on clinical data, 240 lung transplant recipients were eligible for CLAD, and HLA and eplet mismatch was analyzed using the HLAMatchmaker 3.1 software. Results: A total of 92 (38.3%) lung transplant recipients developed CLAD. The time free-of-CLAD was significantly decreased in patients with presence of DQA1 eplet mismatches (P = 0.015). Furthermore, when other previously described CLAD risk factors were studied in a multivariate analysis, the presence of DQA1 eplet mismatches was found to be independently associated with the early onset of CLAD. Conclusions: The concept of epitope load has arisen as a new tool to better define donor-recipient immunologic compatibility. The presence of DQA1 eplet mismatches potentially would increase the likelihood of developing CLAD.

CD64 expression on neutrophils as a potential biomarker for bacterial infection in ascitic fluid of cirrhotic patients.

BACKGROUND: CD64 expression on neutrophils surface (CD64N) by flow cytometry has been validated as a rapid biomarker for bacterial infections in both peripheral blood and other biological fluids. Ascites is a common complication in cirrhotic patients that a variety of factors can cause, including bacterial infections. Manual counting of polymorphonuclear (PMN) cells in ascitic fluid and microbiologic culture are essential for its diagnosis. We aimed to validate the determination of CD64N by flow cytometry in ascitic fluid and assess its potential usefulness in the rapid identification of bacterial infections. MATERIALS AND METHODS: A prospective unicentre study was conducted. Flow cytometry was used to analyse the expression of CD64N in 77 ascitic fluid samples from the initial paracentesis of 60 cirrhotic patients in different admission episodes from November 2021 to December 2022. RESULTS: Seventeen samples were diagnosed with bacterial infection based on a positive microbiologic culture or by PMN count (>250 PMN/mm3 in ascitic fluid). The median of CD64N MFI was significantly increased in the bacterial infection group (3690.5 MFI [1635.23-6521.18] vs. 1105.9 MFI [737.3-2048.2], p < 0.001). The CD64 MFI ratio of granulocytes to lymphocytes was elevated in the bacterial infection group (13.06 [6.38-24.58] vs. 5.01 [3.38-7.36], p < 0.001). A CD64N ratio higher than 9.9 identified those patients with bacterial infection with 70.6 and 86.7% sensitivity and specificity, with an area under the curve (AUC) of 79.4%. CONCLUSION: The CD64N determined by flow cytometry on ascitic fluid could help quickly identify bacterial infections in ascites patients, allowing early antibiotic treatment.

Laboratory and clinical practices in antinuclear antibody detection and related antigens: recommendations from a Spanish multicentre survey.

Antinuclear antibodies (ANA) are the most widely used immunological test for the diagnosis of autoimmune diseases. Despite the recommendations of experts, there is some variability in performing and interpreting this test in routine practice. In this context, the Spanish Group on Autoimmune Diseases (GEAI) of the Spanish Society of Immunology (SEI) conducted a national survey of 50 autoimmunity laboratories. Here we report the survey results on ANA testing, detection of related antigens, and our recommendations. The survey showed that most of the participating laboratories use a similar approach for most key practices: 84% perform ANA by indirect immunofluorescence (IIF) on HEp-2 cells as the screening methodology while the other laboratories use IIF to confirm positive screens; 90% report ANA test results as either negative or positive with titer and pattern; 86% indicated that the ANA pattern conditioned follow-up testing for specific antigen-related antibodies; and 70% confirm positive anti-dsDNA. However, testing practices were highly heterogeneous for certain items, such as sera dilutions and the minimum time period for repeating ANA and related antigen determinations. Overall, this survey shows that most autoimmune laboratories in Spain use a similar approach but that further standardization of testing and reporting protocols is needed.

Comparison of ANA testing by indirect immunofluorescence or solid-phase assays in a low pre-test probability population for systemic autoimmune disease: the Camargo Cohort.

OBJECTIVES: Autoantibodies and, specifically antinuclear antibodies (ANA), are the hallmark of systemic autoimmune diseases (AID). In the last decades, there has been great technical development to detect these autoantibodies along with an increased request for this test by clinicians, while the overall pre-test probability has decreased. In this study, we compare the diagnostic performance of three different methods for ANA screening (indirect immunofluorescence [IIF], addressable laser bead immunoassay [ALBIA], and fluorescence enzyme immunoassay [FEIA]). METHODS: Serum samples at baseline visit from 2,997 participants from the Camargo Cohort, a population with an overall low pre-test probability for systemic AID, were analyzed with the three methods. Participants have a minimum follow-up of 10 years and the development of autoimmune diseases was collected from clinical records. RESULTS: The highest frequency of positive ANA was observed by IIF assay. However, ALBIA showed high sensitivity for AID. Likewise, solid phase assays (SPA) presented higher specificity than IIF for AID. ANA prevalence with any method was significantly higher in females and overall increased with age. Triple positivity for ANA was significantly related to the presence of anti-dsDNA-SSA/Ro60, Ro52, SSB/La, RNP, Scl-70, and centromere-specificities. No association was found for anti-Sm - RNP68, or ribosomal P - specificities. Noteworthy, triple positivity for ANA screening was associated with diagnosis of systemic AID both at baseline visit and follow-up. CONCLUSIONS: ANA detection by IIF may be better when the pre-test probability is high, whereas SPA techniques are more useful in populations with an overall low pre-test probability for systemic AID.

Development of SARS-CoV-2 specific IgG and IgA antibodies in serum and milk with different SARS-COV-2 vaccines in lactating women.

BACKGROUND: Our main objective was to determine the evolution of IgG and IgA antibodies directed against SARS-CoV-2 protein S in the blood of lactating women and in breast milk. METHODS: A cohort of 110 uninfected and vaccinated breastfeeding women was followed-up for 6 months at the Marqués de Valdecilla University Hospital, Spain, in 2020. An additional group of 23 breastfeeding mothers who had no previously documented infection and had not been vaccinated against SARS-CoV-2 were included as a control group. The antibodies in blood and breast milk and their evolution at 6 months post-vaccination were analysed. RESULTS: One hundred ten breastfeeding mothers were included; 70 women (63.6%) were vaccinated with two doses of BNT162b2, 20 women (18.2%) received two doses of mRNA-1273, and 20 women (18.2%) received a single dose of ChAdOx1-S. No evidence of differences between concentrations of antibodies was found according to the type of vaccine, with the exception of serum IgA antibodies, which was higher in women vaccinated with mRNA-1273: mean [95%CI]: 0.05 AU/mL [0.03,0.06] with mRNA-1273, 0.02 AU/mL [0.01,0.03] with BNT162b2 and 0.01 AU/mL [0.00,0.03] with ChAdOx1-S, ANOVA p value = 0.03. The lack of difference between vaccines was also found when anti-S1 specific IgG in serum and breast milk were measured. CONCLUSIONS: In lactating women vaccinated against COVID-19, anti-SARS-CoV-2 antibodies can be detected in both serum and breastmilk 6 months after receiving the second dose, although their concentrations decreased when compared with concentrations reached immediately after vaccination.

Non-HLA Antibodies and Their Role in Highly Sensitized Patients.

BACKGROUND: The role of non-HLA antibody is gaining special attention in solid-organ transplantation and in highly sensitized (HS) patients because of its potential involvement in graft loss (GL) and/or antibody-mediated rejection (ABMR). The identification of non-HLA antibodies while listed may provide deeper information about the increased immunologic risk prior to transplant. We aimed to identify non-HLA antibodies pretransplant that could involve GL in HS patients. METHODS: Nineteen pretransplant samples from HS patients who underwent transplant at the Marqués de Valdecilla University Hospital were studied for both HLA antibodies and a panel of 39 non-HLA antigens analyzed based on Luminex platform. RESULTS: Eleven patient (57.9%) maintained the graft (KT group), whereas 8 (42.1%) had a GL within a median of 30 days. The median fluorescent intensity (MFI) of the 39 non-HLA antigens were compared within the groups, obtaining a statistically significant differences in protein tyrosine phosphatase receptor type N (P < .04) with a MFI mean of 1408 vs 4931 for KT and GL groups, respectively. However, no significant differences were observed in non-HLA MFI between ABMR and non-ABMR KT recipients. CONCLUSIONS: The presence of non-HLA antibodies in HS is high. The levels of anti-protein tyrosine phosphatase receptor type N before transplant could indicate a potential risk of GL, although longitudinal studies with large number of cases are needed to define anti-non-HLA profiles of risk of ABMR.

Estimation of Antibody-Verified Eplet Mismatch Load, 2-Field HLA Resolution vs Imputation in a Large Cohort of European Donors.

BACKGROUND: The assessment of class II eplet mismatch load is useful to determine the risk of chronic rejection in solid organ transplantation. However, high-resolution (2-field) HLA typing is mandatory to accurately define eplet mismatches. The imputation of the most frequent allele has been used in retrospective studies. Here, we sought to investigate the concordant of antibody-verified (AbV) eplet load in different class II alelles between real 2-field HLA typing and HLA imputed by most frequent allele in a large White cohort. MATERIALS AND METHODS: The allelic frequency of the different HLA class II loci was calculated using a database of high-resolution typing of 23,628 voluntary Spanish bone marrow donors obtained from the Spanish Registry of Bone Marrow Donors, managed by the Josep Carreras Foundation. The AbV eplet count in the different class II alleles was performed using the HLA-Matchmaker v3.1 algorithm. RESULTS: The probability of imputing the correct allele compared to the most frequent for DRB1 and DQB1 loci was 69.3% and 53.0%, respectively. However, studying the less frequent alleles, the same AbV eplet load was observed in 82.22% and 76.15%, respectively. CONCLUSIONS: Our data show that despite the potential error in the imputation of class II HLA typing, the number of AbV eplets is not significantly over- or underestimated in our population. Until high-resolution typing is widely established for solid organ transplantation, retrospective studies of AbV eplet mismatch load with imputed high-resolution types provide an acceptable outcome in White people.

Increased induction of de novo serum ANCA and ANCA-associated vasculitis after mass vaccination against SARS-CoV-2.

Different immune-mediated diseases have been described after SARS-CoV-2 vaccination, with antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) being one of the possible side effects. In this study, a total of 35 patients presented ANCA for the first time during 2021, with the number during 2019 being 15. Twenty-seven out of thirty-five patients developed ANCA after vaccination. Two of them developed these antibodies after receiving the first dose (7.4%), and 25 patients developed ANCA after the second dose of the vaccine (92.6%), with BNT162b2 being the main vaccine received by these patients. In 97.1% of the patients who developed ANCA during 2021, the positivity of ANCA was accompanied by systemic involvement, with renal and respiratory tracts being the main organs affected. Therefore, an increase in the development of AAV has been observed during 2021 in comparison with 2019, which could be due to the administration of SARS-CoV-2 vaccine.

Neddylation tunes peripheral blood mononuclear cells immune response in COVID-19 patients.

The COVID-19 pandemic caused by SARS-CoV-2 has reached 5.5 million deaths worldwide, generating a huge impact globally. This highly contagious viral infection produces a severe acute respiratory syndrome that includes cough, mucus, fever and pneumonia. Likewise, many hospitalized patients develop severe pneumonia associated with acute respiratory distress syndrome (ARDS), along an exacerbated and uncontrolled systemic inflammation that in some cases induces a fatal cytokine storm. Although vaccines clearly have had a beneficial effect, there is still a high percentage of unprotected patients that develop the pathology, due to an ineffective immune response. Therefore, a thorough understanding of the modulatory mechanisms that regulate the response to SARS-CoV-2 is crucial to find effective therapeutic alternatives. Previous studies describe the relevance of Neddylation in the activation of the immune system and its implications in viral infection. In this context, the present study postulates Neddylation, a reversible ubiquitin-like post-translational modification of proteins that control their stability, localization and activity, as a key regulator in the immune response against SARS-CoV-2. For the first time, we describe an increase in global neddylation levels in COVID-19 in the serum of patients, which is particularly associated with the early response to infection. In addition, the results showed that overactivation of neddylation controls activation, proliferation, and response of peripheral blood mononuclear cells (PBMCs) isolated from COVID-19 patients. Inhibition of neddylation, and the subsequent avoidance of activated PBMCs, reduces cytokine production, mainly IL-6 and MCP-1 and induce proteome modulation, being a critical mechanism and a potential approach to immunomodulate COVID-19 patients.

The Past, Present, and Future in Antinuclear Antibodies (ANA).

Autoantibodies are a hallmark of autoimmunity and, specifically, antinuclear antibodies (ANAs) are the most relevant autoantibodies present in systemic autoimmune rheumatic diseases (SARDs). Over the years, different methods from LE cell to HEp-2 indirect immunofluorescence (IIF), solid-phase assays (SPAs), and finally multianalyte technologies have been developed to study ANA-associated SARDs. All of them provide complementary information that is important to provide the most clinically valuable information. The identification of new biomarkers together with multianalyte platforms will help close the so-called "seronegative gap" and to correctly classify and diagnose patients with SARDs. Finally, artificial intelligence and machine learning is an area still to be exploited but in a next future will help to extract patterns within patient data, and exploit these patterns to predict patient outcomes for improved clinical management.

Disease criteria of systemic lupus erythematosus (SLE); the potential role of non-criteria autoantibodies.

Patients with SLE show a broad spectrum of more than 200 autoantibodies. They can be pathogenic, predictive, prognostic or even an epiphenomenon. Here, we discuss different autoantibodies that have not been included in EULAR/ACR 2019 classification criteria. Most of them have been addressed to monitor and detect disease activity and not specifically as classification criteria. Indeed, markers to assess disease activity fluctuate as compared with classification criteria and their validation is different. The development of new methods will probably bring new clinical associations and be evaluated as potential classification criteria.