Helper T cell immunity in humans with inherited CD4 deficiency.

CD4+ T cells are vital for host defense and immune regulation. However, the fundamental role of CD4 itself remains enigmatic. We report seven patients aged 5-61 years from five families of four ancestries with autosomal recessive CD4 deficiency and a range of infections, including recalcitrant warts and Whipple's disease. All patients are homozygous for rare deleterious CD4 variants impacting expression of the canonical CD4 isoform. A shorter expressed isoform that interacts with LCK, but not HLA class II, is affected by only one variant. All patients lack CD4+ T cells and have increased numbers of TCRαß+CD4-CD8- T cells, which phenotypically and transcriptionally resemble conventional Th cells. Finally, patient CD4-CD8- αß T cells exhibit intact responses to HLA class II-restricted antigens and promote B cell differentiation in vitro. Thus, compensatory development of Th cells enables patients with inherited CD4 deficiency to acquire effective cellular and humoral immunity against an unexpectedly large range of pathogens. Nevertheless, CD4 is indispensable for protective immunity against at least human papillomaviruses and Trophyrema whipplei.

Anti-titin antibodies in a cohort of myasthenia gravis patients.

Background: Anti-titin antibodies have been previously associated with thymoma-associated myasthenia gravis (MG) and a more clinically severe form of MG. While currently only serving as a disease biomarker, its possible utility as an indicator of underlying thymus malignancy may be of value in clinical practice. Methods: Data was retrospectively collected and analyzed from 2013 to 2022 using an institutional record of MG patients. Anti-titin antibodies were assessed using Line Blot immunoassay. Results: From 130 MG cases, 32 (24.6%) were anti-titin positive. Anti-titin positive cases were associated with older age of disease onset [median (IQR): 63.0 (44.3-70.8) vs. 35.5 (24.8-60.8) years] (P<0.01). Thymectomy was performed in 46 (35.4%) MG patients, 12 of which anti-titin positive (26.1%). Thymectomy samples from anti-titin positive patients comprised 10 (83.3%) cases of thymoma and 2 (16.7%) cases of thymus hyperplasia. There was a tendency towards anti-titin positive patients having more thymoma while anti-titin negative displayed more hyperplasia (P<0.01). Anti-titin positivity correlated with thymoma in patients with age of onset bellow 50 years (P=0.028). Anti-titin positivity was significantly associated with generalized MG in the late-onset group (P=0.005). Conclusions: The presence of anti-titin antibodies appears to correlate with underlying thymoma in early-onset MG cases and with generalized MG in late-onset cases. Prospective studies are needed to further study this association.

Exploring gastric cancer genetics: A turning point in common variable immunodeficiency.

Background: Gastric cancer (GC) stands as a prominent cause of cancer-related mortality and ranks second among the most frequently diagnosed malignancies in individuals with common variable immunodeficiency (CVID). Objective: We sought to conduct a comprehensive, large-scale genetic analysis to explore the CVID-associated germline variant landscape within gastric adenocarcinoma samples and to seek to delineate the transcriptomic similarities between GC and CVID. Methods: We investigated the presence of CVID-associated germline variants in 1591 GC samples and assessed their impact on tumor mutational load. The progression of GC was evaluated in patients with and without these variants. Transcriptomic similarities were explored by matching differentially expressed genes in GC to healthy gastric tissue with a CVID transcriptomic signature. Results: CVID-associated germline variants were found in 60% of GC samples. Our analysis revealed a significant association between the presence of CVID-related genetic variants and higher tumor mutational load in GC (P < .0001); high GC mutational load seems to be linked to immunotherapy response and worse prognosis. Transcriptomic similarities unveiled key genes and pathways implicated in innate immune responses and tumorigenesis. We identified upregulated genes related to oncogene drivers, inflammation, tumor suppression, DNA repair, and downregulated immunomodulatory genes shared between GC and CVID. Conclusions: Our findings contribute to a deeper understanding of potential molecular modulators of GC and shed light on the intricate interplay between immunodeficiency and cancer. This study underscores the clinical relevance of CVID-related variants in influencing GC progression and opens avenues for further exploration into novel therapeutic approaches.

Blood and CSF anti-neuronal antibodies testing in psychotic syndromes: a retrospective analysis from a tertiary psychiatric hospital.

A Consensus of Psychoimmunology Experts (Pollak et al., 2019) established a set of red flags and proposed diagnostic criteria for psychosis of autoimmune origin (AIP). Previous studies on AIP are limited by the scarcity of CSF analysis, preventing the valorization of blood anti-neuronal antibodies (Ab). The aims of this study are to determine the relative frequency and characterize AIP in a cohort of psychotic patients that underwent CSF workup. This work is a retrospective study in a tertiary psychiatric hospital. Clinical and paraclinical data were collected from medical records, and patients were classified according to Pollak et al. (2019) criteria. From 68 patients, ten (14.7%) had positive anti-neuronal antibodies (Ab): n = 5 in CSF and blood (n = 4 anti-NMDAr, n = 1 -GAD65), and n = 5 in blood only (n = 1 anti-GABAb, n = 1 -GAD65, n = 1 -SOX1, n = 1 -NMDAr, n = 1 -zic4). After 5- (2-10)-year follow-up, n = 6/68 (8.8%) had AIP diagnosis in context of autoimmune encephalitis (AE), and the remaining (n = 4/10, blood-only Ab) alternative diagnoses (n = 2 dementia, n = 1 schizophrenia, n = 1 intellectual disability). Ten of the 13 patients that fulfilled criteria for possible AIP were mimics, and only three AE had criteria for probable AIP. All AIP developed neurological manifestations (mostly cognitive dysfunction); EEG was usually abnormal (66.7%), and all had normal MRI. We found statistically significant associations between AIP/AE and systemic autoimmune disease, presentation with seizures and EEG abnormalities. All AE developed neurological symptoms alongside psychosis. Ab positivity occurred predominantly in AE but also in other neuropsychiatric disorders. Clinical suspicion based on the knowledge of the described presentations of established Ab is crucial in the psychotic patient approach.

Distinct phenotypes in a cohort of anti-CASPR2 associated neurological syndromes.

INTRODUCTION: Anti-contactin-associated protein-like 2 (CASPR2) is classically associated with limbic encephalitis (LE), Morvan syndrome and peripheral nerve hyperexcitability (PNH). Additional clinical features have been previously recognized. OBJECTIVE: To describe a cohort of patients with anti-CASPR2-associated neurological syndromes from a tertiary referral centre. METHODS: Retrospective analysis of patients with positive serum anti-CASPR2 antibodies in the period between 2014 and 2021. RESULTS: Nineteen patients were identified, 11 (57.9%) male, with a median age at symptom onset of 49.0 (31.3-63.0) years and a median time to diagnosis of 1.0 (0.0-1.8) years. The most common clinical syndromes were LE (7 cases, 36.8%), Morvan syndrome (4, 21.1%) and PNH (2, 10.5%). Six patients presented with atypical phenotypes (31.6%), comprising dysautonomia (orthostatic hypotension and Adie's Pupil), motor tics/stereotypies, obsessive-compulsive disorder, and brainstem involvement. The most common presenting symptoms were seizures (31.6%), PNH (21.1%) and cognitive dysfunction (15.8%). One LE patient had a disease duration of 2,5 years and was initially diagnosed with dementia. CSF was normal in most cases. Brain MRI showed temporal lobe hyperintensities in 4 LE cases (57.1%). All PNH cases had myokymic discharges of fasciculations in the electromyography. Two patients had associated thymoma and 1 had lung adenocarcinoma. Eight patients (42.1%) received treatment during the acute phase and 26.3% maintenance treatment. Approximately half of the treated cases improved or stabilised, with 4 (21.1%) deaths in the whole cohort. CONCLUSION: Anti-CASPR2-associated neurological disorders may present with isolated atypical phenotypes, a slowly progressive clinical course, and with normal CSF or imaging findings.

Th17 / Treg ratio: A prospective study in a group of pregnant women with preeclampsia and fetal growth restriction.

INTRODUCTION: During pregnancy, the maternal immune system is challenged to tolerate a semi-allogenic fetus. A proinflammatory profile has been linked to adverse pregnancy outcomes and poor placental development. In this study, the authors evaluated the number of circulating Tregs and Th17 cells in a group of patients diagnosed with preeclampsia(PE) and fetal growth restriction(FGR). METHODS: Prospective longitudinal observational study where peripheral blood lymphocyte subsets were analyzed in a cohort of pregnant patients with PE, FGR, and a control group of healthy pregnant women. RESULTS: The diagnosis of PE was associated with a significative higher number of circulating Th17 cells and a significative relative reduction in the Treg cell count. This proinflammatory profile was also expressed in the evolution of the Th17/ CD4+CD25highFOXP3+ Treg ratio. In the FGR group, the Th17 cell count was significantly higher during the third trimester of pregnancy. This proinflammatory profile was also expressed in the evolution of the Th17/ CD4+CD25highFOXP3+ Treg ratio. When we compare the immunological profiles of patients with PE and FGR we observed a higher number of proinflammatory Th17 cells and a significative lower number of Treg cells in PE patients. This is particularly expressed in the differences found between the Th17/ CD4+CD25highFOXP3+ Treg ratios of these two groups. Discussion/Conclusion Our data showed a that a proinflammatory profile and a relative excess of Th17 cells was associated with the diagnosis of PE and FGR. A more exuberant systemic proinflammatory profile present in the PE patients is absent in patients with FGR without preeclampsia.

Genomic crossroads between non-Hodgkin's lymphoma and common variable immunodeficiency.

Common variable immunodeficiency (CVID) represents the largest group of primary immunodeficiencies that may manifest with infections, inflammation, autoimmunity, and cancer, mainly B-cell non-Hodgkin's lymphoma (NHL). Indeed, NHL may result from chronic or recurrent infections and has, therefore, been recognized as a clinical phenotype of CVID, although rare. The more one delves into the mechanisms involved in CVID and cancer, the stronger the idea that both pathologies can be a reflection of the same primer events observed from different angles. The potential effects of germline variants on specific somatic modifications in malignancies suggest that it might be possible to anticipate critical events during tumor development. In the same way, a somatic alteration in NHL could be conditioning a similar response at the transcriptional level in the shared signaling pathways with genetic germline alterations in CVID. We aimed to explore the genomic substrate shared between these entities to better characterize the CVID phenotype immunodeficiency in NHL. By means of an in-silico approach, we interrogated the large, publicly available datasets contained in cBioPortal for the presence of genes associated with genetic pathogenic variants in a panel of 50 genes recurrently altered in CVID and previously described as causative or disease-modifying. We found that 323 (25%) of the 1,309 NHL samples available for analysis harbored variants of the CVID spectrum, with the most recurrent alteration presented in NHL occurring in PIK3CD (6%) and STAT3 (4%). Pathway analysis of common gene alterations showed enrichment in inflammatory, immune surveillance, and defective DNA repair mechanisms similar to those affected in CVID, with PIK3R1 appearing as a central node in the protein interaction network. The co-occurrence of gene alterations was a frequent phenomenon. This study represents an attempt to identify common genomic grounds between CVID and NHL. Further prospective studies are required to better know the role of genetic variants associated with CVID and their reflection on the somatic pathogenic variants responsible for cancer, as well as to characterize the CVID-like phenotype in NHL, with the potential to influence early CVID detection and therapeutic management.

Late onset neuromyelitis optica spectrum disorders (LONMOSD) from a nationwide Portuguese study: Anti-AQP4 positive, anti-MOG positive and seronegative subgroups.

INTRODUCTION: Several neuroimmunological disorders have distinct phenotypes according to the age of onset, as in multiple sclerosis or myasthenia gravis. It is also described that late onset NMOSD (LONMOSD) has a different phenotype. OBJECTIVE: To describe the clinical/demographic characteristics of the LONMOSD and distinguish them from those with early onset (EONMOSD). METHODS: From a nationwide Portuguese NMOSD study we analyzed the clinical/demographic characteristics of the LONMOSD. RESULTS: From the 180 Portuguese patients 45 had disease onset after 50 years old, 80% were female. 23 had anti-AQP4 antibodies (51.1%), 13 anti-MOG antibodies (28.9%) and 9 were double seronegative (20.0%). The most common presenting phenotypes in LONMOSD were transverse myelitis (53.3%) and optic neuritis (26.7%), without difference from EONMOSD (p = 0.074). The mean EDSS for LONMOSD was 6.0 (SD=2.8), after a mean follow-up time of 4.58 (SD=4.47) years, which was significantly greater than the mean EDSS of EONMOSD (3.25, SD=1.80)(p = 0.022). Anti-AQP4 antibodies positive LONMOSD patients had increased disability compared to anti-MOG antibodies positive LONMOSD (p = 0.022). The survival analysis showed a reduced time to use a cane for LONMOSD, irrespective of serostatus (p<0.001). CONCLUSIONS: LONMOSD has increased disability and faster progression, despite no differences in the presenting clinical phenotype were seen in our cohort.

The dynamics of Th17 / Treg ratio in SLE patients during pregnancy.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder that affects women at childbearing age. During pregnancy, maternal immune system is challenged to tolerate a semi-allogenic fetus and a shift toward a tolerogenic profile is essential. Failure to develop this tolerogenic profile seems to be associated with the development of adverse obstetric outcomes. We conducted a prospective longitudinal observational study where peripheral blood lymphocyte subsets were analyzed during pregnancy in a group of SLE patients and compared with healthy gestations. We observed a reduction in peripheric Treg cell count throughout all pregnancy in control patients, which was not observed in SLE patients. In contrast, the Th17 cell count remained stable in both groups. In the control group, the Treg/Th17 ratio decreased throughout pregnancy to the postpartum, which was not observed in the study group. These changes may be justified by the migration of the immunotolerant Treg cells to the maternal decidua and may lead to the establishment of a pro-inflammatory profile by the end of pregnancy in healthy pregnancies, which was not observed in the SLE pregnant patients. This pro-inflammatory state at the end of a healthy pregnancy may be necessary for the spontaneous beginning of labor and help to explain why systemic syndromes like preeclampsia develop during the second half of pregnancy. The lack of these findings in SLE patients may express a pro-inflammatory state from the beginning of pregnancy, the influence of immunomodulatory medication or an intrinsic deregulation of immune function, which is a characteristic of these patients.

Anti-NMDAr Encephalitis and COVID-19 in a Patient With Systemic pANCA-Vasculitis and Recurrent Varicella Zoster Infection.

Introduction: There is a complex interplay between systemic autoimmunity, immunosuppression, and infections. Any or all of these can result in neurologic manifestations, requiring diligence on the part of neurologists. Case report: We herein report a case of a patient on immunosuppressive treatment for a vasculitis that resulted in zoster meningoencephalitis. This was further complicated by the development of anti-NMDAr encephalitis, the etiology of which is undetermined and further discussed in this paper. The patient eventually developed COVID-19 during hospitalization, succumbing to the respiratory infection. Conclusion: This case emphasizes that post-infectious autoimmune disorders are becoming increasingly recognized and that they should still be considered in patients who are on immunosuppression. Practitioners should be aware of the complex relationship between autoimmunity and immunosuppression and consider both throughout the disease course.

Autoimmune encephalitis: suspicion in clinical practice and mimics.

Despite the existence of well-established diagnostic criteria for autoimmune encephalitis, there are diseases capable of mimicking it. This study sought to retrospectively evaluate the reasons for testing and the final diagnosis of patients admitted to a Neurology ward tested for anti-NMDAR antibodies and estimate sensitivity and specificity of current diagnostic criteria. The threshold for testing was lower than that of the prevailing diagnostic criteria, and the proportion of autoimmune encephalitis mimics was high. Searching for alternative diagnoses is of pivotal importance in cases of autoimmune encephalitis suspicion, and diagnostic criteria may need expanding so that no autoimmune encephalitis is missed.

Kappa free light chains: Diagnostic performance in multiple sclerosis and utility in a clinical laboratory.

BACKGROUND: Automated, technically simple analytical methods offering objective results are highly valued in clinical laboratories. Kappa free light chains (KFLC) in cerebrospinal fluid (CSF) are promising multiple sclerosis (MS) biomarkers, particularly kappa (K) index. METHODS: KFLC were determined in CSF and serum samples of patients diagnosed with MS, clinically/radiologically isolated syndrome (N, 39), and controls (N, 152; inflammatory and non-inflammatory neurological disorders). Diagnostic performance of several KFLC parameters, previously determined oligoclonal band (OCB) testing, and IgG index, was assessed. A K index decision threshold for sample screening was identified and reduction in performed OCB analyses estimated accordingly. RESULTS: Higher KFLC parameters were detected in the MS group and K index performed best among them (AUC 0.92). At a 7.25 cut-off it showed better sensitivity (85% vs. 77%) though less specificity (88% vs. 91%) than OCBs. Comparatively, IgG index's performance was inferior (AUC 0.83). A decision K index threshold of 2.55 (97% sensitivity) would reduce OCB testing by 52% in the studied population. CONCLUSIONS: The proposed 7.25 cut-off could assist MS diagnostics and identify some false negative cases from OCB studies. Sequential algorithms using K index for the decision to perform OCB detection would improve laboratory efficiency and substantially reduce costs.

Systemic Lupus Erythematosus and Pregnancy: a Portuguese Case-Control Study.

Pregnancy in systemic lupus erythematosus (SLE) patients is associated with an increased risk of adverse outcomes. During pregnancy, SLE patients have a higher rate of miscarriage, stillbirth, preterm delivery, fetal growth restriction, or hypertensive disorders of pregnancy. To date, only a few case-control studies were published with the purpose to evaluate the magnitude of risk associated with pregnancy in lupus patients. The aim of our study was to evaluate the maternal and fetal outcomes in a cohort of Portuguese SLE patients and to compare it with a group of healthy pregnant women. We conducted a retrospective case-control study that included all pregnant women with SLE managed at a Portuguese tertiary center, between 2010 and 2019. Pregnancy outcomes were compared between SLE patients and a group of matched healthy pregnant women. Baseline maternal data was collected, and maternal-fetal and neonatal outcomes were evaluated. One hundred twenty-four SLE pregnancies were included. Of the patients, 95.2% were in remission at conception. In 13.7% of cases, a lupus flare was diagnosed during gestation and in 17.9% in the postpartum period. The live birth rate was 84.6%, and the incidence of adverse outcomes was 40.3% (OR 2.64, 95% CI 1.67-4.18). Considering only patients in remission at conception, the presence of adverse outcomes remained significantly higher (36.8% vs. 20.3%, P < 0.01). Miscarriage rate was 15.3% (OR 5.85, 95% CI 2.57-13.34) and preterm delivery occurred in 12.4% of the patients (OR 1.72, 95% CI 0.83-3.57). Preeclampsia prevalence was higher in SLE patients (OR 3.92, 95% CI 1.32-11.57). In the SLE group, the newborn admission to an intensive care unit rate was increased (OR 4.99, 95% CI 1.47-16.90). No neonatal or maternal deaths were reported. In our study, pregnancy with SLE was associated with an increased incidence of adverse outcomes, even in a population of SLE patients with well-controlled disease.

Systemic lupus erythematosus and pregnancy: A retrospective single-center study of 215 pregnancies from Portugal.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a life-threatening disorder that affects women at reproductive age. We evaluate the clinical impact of pregnancy in a cohort of Portuguese SLE patients and the risk factors associated with maternal and fetal adverse outcomes. METHODS: A retrospective observational study that included all pregnant women with SLE managed at a Portuguese tertiary hospital, between January 1993 and December 2019. Baseline maternal information was collected, and maternal-fetal and neonatal outcomes were evaluated. Disease activity before and during pregnancy was assessed. RESULTS: We included 215 pregnancies from 143 patients. Lupus nephritis was present in 20.0% and antiphospholipid syndrome (APS) in 21.9% of the cases. Preconception consultation was performed in 86.9% of the pregnancies, and 92.5% of the patients had no or low disease activity at conception. During gestation, 79.6% of the patients were under treatment, and hydroxychloroquine (HCQ) was the most commonly used drug (63.7%). Low-dose acetylsalicylic acid (ASA) was prescribed at conception in 87.9% of the patients. The live birth rate was 84.2%. An adverse pregnancy outcome (APO) occurred in 41.4% of the pregnancies. A miscarriage rate of 15.3% and a preterm delivery rate of 15.4% were found. Preeclampsia and fetal growth restriction complicated 13.1% and 14.0% of the gestations, respectively. Neonatal lupus occurred in 7.1% of the newborns, and there were 2 cases of congenital heart block. Significant risk factors for the development of AOP were disease activity at conception, lupus flare, hypocomplementemia, positivity for lupus anticoagulant, and APS. The use of ASA was significantly associated with a reduced incidence of miscarriage. An SLE flare was diagnosed in 16.3% of the cases. We identified as risk factors for lupus flares the presence of active disease at conception, a previous history of lupus nephritis, and the use of chronic medication. HCQ use during pregnancy was associated with a significant reduction of flare incidence during pregnancy and postpartum. CONCLUSIONS: Pregnancy in an SLE patient is associated with an increased incidence of adverse obstetric outcomes. Good disease control before pregnancy and adequate treatment, especially with HCQ, is crucial to achieving the best obstetric results.

Neuromyelitis optica spectrum disorders: A nationwide Portuguese clinical epidemiological study.

INTRODUCTION: Neuromyelitis optica spectrum disorder (NMOSD) is a rare disorder in which astrocyte damage and/or demyelination often cause severe neurological deficits. OBJECTIVE: To identify Portuguese patients with NMOSD and assess their epidemiological/clinical characteristics. METHODS: This was a nationwide multicenter study. Twenty-four Portuguese adult and 3 neuropediatric centers following NMOSD patients were included. RESULTS: A total of 180 patients met the 2015 Wingerchuk NMOSD criteria, 77 were AQP4-antibody positive (Abs+), 67 MOG-Abs+, and 36 seronegative. Point prevalence on December 31, 2018 was 1.71/100,000 for NMOSD, 0.71/100,000 for AQP4-Abs+, 0.65/100,000 for MOG-Abs+, and 0.35/100,000 for seronegative NMOSD. A total of 44 new NMOSD cases were identified during the two-year study period (11 AQP4-Abs+, 27 MOG-Abs+, and 6 seronegative). The annual incidence rate in that period was 0.21/100,000 person-years for NMOSD, 0.05/100,000 for AQP4-Abs+, 0.13/100,000 for MOG-Abs+, and 0.03/100,000 for seronegative NMOSD. AQP4-Abs+ predominated in females and was associated with autoimmune disorders. Frequently presented with myelitis. Area postrema syndrome was exclusive of this subtype, and associated with higher morbidity/mortality than other forms of NMOSD. MOG-Ab+ more often presented with optic neuritis, required less immunosuppression, and had better outcome. CONCLUSION: Epidemiological/clinical NMOSD profiles in the Portuguese population are similar to other European countries.

Stem cell transplantation as treatment for major histocompatibility class I deficiency.

Major histocompatibility class I deficiency, due to genetic lesions in TAP1, TAP2, TAPBP, or B2M, manifests with recurrent sinopulmonary infections and granulomatous skin ulceration, and is predominately treated with antimicrobial prophylaxis and chest physiotherapy. One previous report of hematopoietic stem cell transplantation has been described in the literature, demonstrating cure of the immune defect without significant graft-versus-host disease. In this report, we expand the literature on HSCT in MHC-I deficiency with follow-up of the original patient, demonstrating maintained resolution of normal immune function and regression of the granulomatous rash 15 years post-transplant, and describe a further patient with mycobacterial disease whose transplant course was complicated by severe graft-versus-host disease.

[International Consensus on Antinuclear Antibody Patterns in Portugal]. / International Consensus on Antinuclear Antibody em Portugal.

INTRODUCTION: Screening for autoantibodies in HEp-2 cells by indirect immunofluorescence is currently accepted as the gold-standard test for the diagnosis of systemic autoimmune diseases. The main objective of the International Consensus on ANA Patterns is to achieve a consensus on the nomenclature and description of antinuclear antibody morphological patterns. This work aims to build on the International Consensus on ANA Patterns project to establish a nomenclature consensus in Portugal, thus contributing to harmonization in autoimmune diagnosis and promoting diagnostic quality in autoimmune systemic rheumatic diseases. MATERIAL AND METHODS: Participating laboratories identified all the nuclear and cytoplasmic pattern designations in the International Consensus on ANA Patterns (including the anti-cell pattern code), and matched them with the corresponding Portuguese nomenclature in use. The results were aggregated and used as a foundation for nomenclature harmonization work. Consensus meetings followed an iterative process, until a final consensual proposal was drafted. RESULTS: Prior agreement between laboratories was over 75% for 23 of the total 29 anti-cell patterns. The degree to which each laboratory is aligned with the International Consensus on ANA Patterns international reference ranges from 22.1% to 100%. It was possible to write a consensual version of the International Consensus on ANA Patterns nomenclature for Portugal. DISCUSSION: There was a good consensus basis for the nomenclature in the International Consensus on ANA Patterns, despite relevant differences with some translations. The study highlights the need for collaboration among laboratories towards an unambiguous description of laboratory results. CONCLUSION: This study shows that there is good potential for collaboration between laboratories in order to produce the consensus needed to improve diagnosis and patient follow-up.

Introdução: A pesquisa de autoanticorpos em células HEp-2 através de imunofluorescência indireta é o teste padrão atualmente aceite como a ferramenta central para o diagnóstico das doenças autoimunes sistémicas. O International Consensus on Antinuclear Antibody (ANA) Patterns tem como objetivo principal alcançar um consenso na nomenclatura e na descrição dos diferentes padrões morfológicos de anticorpos antinucleares. Este trabalho tem como objetivo ampliar o projeto do International Consensus on ANA Patterns de forma a estabelecer um consenso em Portugal para a sua nomenclatura, procurando contribuir para a harmonização no diagnóstico autoimune e promover a qualidade diagnóstica nas doenças reumáticas sistémicas autoimunes.Material e Métodos: Os laboratórios participantes identificaram cada designação de padrão citoplasmático e nuclear do International Consensus on ANA Patterns (incluindo o código padrão anti-célula), e fizeram corresponder a cada uma a respetiva nomenclatura portuguesa em uso. Os resultados foram agregados e serviram de base ao trabalho de harmonização da nomenclatura. Seguiram-se reuniões de consenso, num processo iterativo até à redação de uma proposta final consensualizada.Resultados: A concordância prévia entre laboratórios era superior a 75% para 23 do total de 29 padrões anti-célula. O grau em que cada laboratório está alinhado com a referência internacional do International Consensus on ANA Patterns varia entre 22,1% e 100%. Foi possível elaborar uma versão consensualizada da nomenclatura do International Consensus on ANA Patterns para Portugal.Discussão: Existia uma boa base de consenso para a nomenclatura do International Consensus on ANA Patterns, mas com diferenças importantes em algumas das traduções da terminologia. O estudo realça a necessidade de colaboração entre laboratórios para uma descrição inequívoca dos resultados laboratoriais.Conclusão: Este trabalho mostra o potencial positivo da colaboração entre laboratórios para gerar consensos que contribuam para a melhoria do diagnóstico e acompanhamento dos doentes.

Variable immunodeficiency score upfront analytical link (VISUAL), a proposal for combined prognostic score at diagnosis of common variable immunodeficiency.

The broad and heterogeneous clinical spectrum that characterizes common variable immunodeficiency (CVID) is associated with quite different disease course and prognosis, highlighting the need to develop tools that predict complications. We developed a multianalyte VISUAL score (variable immunodeficiency score upfront analytical link) aimed to predict severity using individual CVID patient data at baseline of a cohort of 50 CVID patients from two different centers in Portugal and Spain. We retrospectively applied VISUAL to the CVID clinical severity scores proposed by Ameratunga and Grimbacher after 15 years follow-up of our cohort. VISUAL score at CVID diagnosis showed adequate performance for predicting infectious and non-infectious severe complications (Cluster B). Compared to switched memory B lymphocyte phenotype alone, VISUAL provided a more accurate identification of clinically meaningful outcome, with significantly higher sensitivity (85% vs 55%, p = 0.01), and negative predictive value (77% vs 58%) and AUC of the ROC curves (0.72 vs 0.64), with optimal cut-off level of 10. For every increase of 1 point in the VISUAL scale, the odds of being in the higher risk category (Cluster B) increased in 1.3 (p = 0.005) for Ameratunga's severity score and 1.26 (p = 0.004) for Grimbacher's severity score. At diagnosis of CVID, VISUAL score ≥ 10 showed 8.94-fold higher odds of severe prognosis than below this threshold. Kaplan-Meier estimates for the VISUAL ≥ 10 points showed significantly earlier progression to Cluster B than those with VISUAL < 10 (p = 0.0002). This prognostic laboratory score might allow close monitoring and more aggressive treatment in patients with scores ≥ 10 on a personalized basis approach. Further studies are needed to prospectively validate VISUAL score.