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ID PMID Title PublicationDate abstract
32035011 Inclusion-body myositis and primary Sjögren syndrome: mechanisms for shared etiologies. 2020 May Herein we report a case of sporadic inclusion-body myositis (sIBM) occurring at an unusually young age in a patient with primary Sjögren syndrome, and use the case to explore possible shared mechanisms for disease susceptibility. Possible factors may include the association of both conditions with the 8.1 ancestral haplotype; the presence of anti-cN1A antibodies, which, although considered specific for sIBM, are also seen in pSS; and the shared association with T-cell large granular lymphocyte leukemia (T-LGLL). Further evaluation of this patient did in fact reveal underlying T-LGLL and mechanisms by which T cells in sIBM may escape immune regulation and contribute to disease phenotype are explored. Despite myofiber infiltration with CD8-positive T cells in sIBM, and, although sIBM is traditionally considered treatment-refractory, we report a significant response to the anti-CD20 monoclonal antibody, rituximab, and discuss possible mechanisms by which this response may be mediated.
32708341 Salivary Biomarkers and Their Application in the Diagnosis and Monitoring of the Most Comm 2020 Jul 21 Saliva is a highly versatile biological fluid that is easy to gather in a non-invasive manner-and the results of its analysis complement clinical and histopathological findings in the diagnosis of multiple diseases. The objective of this review was to offer an update on the contribution of salivary biomarkers to the diagnosis and prognosis of diseases of the oral cavity, including oral lichen planus, periodontitis, Sjögren's syndrome, oral leukoplakia, peri-implantitis, and medication-related osteonecrosis of the jaw. Salivary biomarkers such as interleukins, growth factors, enzymes, and other biomolecules have proven useful in the diagnosis and follow-up of these diseases, facilitating the early evaluation of malignization risk and the monitoring of disease progression and response to treatment. However, further studies are required to identify new biomarkers and verify their reported role in the diagnosis and/or prognosis of oral diseases.
32896698 Cryoglobulinemic vasculitis in primary Sjögren's Syndrome: Clinical presentation, associa 2020 Oct OBJECTIVE: To describe the clinical spectrum of cryoglobulinemic vasculitis (CV) in primary Sjögren's syndrome (pSS), investigate its relation to lymphoma and identify the differences with hepatitis C virus (HCV) related CV. METHODS: From a multicentre study population of consecutive pSS patients, those who had been evaluated for cryoglobulins and fulfilled the 2011 classification criteria for CV were identified retrospectively. pSS-CV patients were matched with pSS patients without cryoglobulins (1:2) and HCV-CV patients (1:1). Clinical, laboratory and outcome features were analyzed. A data driven logistic regression model was applied for pSS-CV patients and their pSS cryoglobulin negative controls to identify independent features associated with lymphoma. RESULTS: 1083 pSS patients were tested for cryoglobulins. 115 (10.6%) had cryoglobulinemia and 71 (6.5%) fulfilled the classification criteria for CV. pSS-CV patients had higher frequency of extraglandular manifestations and lymphoma (OR=9.87, 95% CI: 4.7-20.9) compared to pSS patients without cryoglobulins. Purpura was the commonest vasculitic manifestation (90%), presenting at disease onset in 39% of patients. One third of pSS-CV patients developed B-cell lymphoma within the first 5 years of CV course, with cryoglobulinemia being the strongest independent lymphoma associated feature. Compared to HCV-CV patients, pSS-CV individuals displayed more frequently lymphadenopathy, type II IgMk cryoglobulins and lymphoma (OR = 6.12, 95% CI: 2.7-14.4) and less frequently C4 hypocomplementemia and peripheral neuropathy. CONCLUSION: pSS-CV has a severe clinical course, overshadowing the typical clinical manifestations of pSS and higher risk for early lymphoma development compared to HCV related CV. Though infrequent, pSS-CV constitutes a distinct severe clinical phenotype of pSS.
32780506 Arginase 1 is involved in lacrimal hyposecretion in male NOD mice, a model of Sjögren's s 2020 Nov KEY POINTS: Few reports have explored the possibility of involvement of non-inflammatory factors in lacrimal hyposecretion in Sjögren's syndrome (SS). RNA-sequencing analysis revealed that only four genes, including arginase 1, were downregulated in the lacrimal gland of SS model male mice (NOD mice) after onset of lacrimal hyposecretion and dacryoadenitis. Even in non-dacryoadenitis-type NOD mice, tear secretion and arginase 1 expression remained low. An arginase 1 inhibitor reduced tear secretion and partially reduced saliva secretion in BALB/c mice. The results indicate that a non-inflammatory factor, arginase 1, is involved in lacrimal hyposecretion in male NOD mice, regardless of dacryoadenitis status. ABSTRACT: Lacrimal fluid (tears) is important for preservation of the ocular surface, and thus lacrimal hyposecretion in Sjögren's syndrome (SS) leads to reduced quality of life. However, the cause(s) of lacrimal hyposecretion remains unknown, even though many studies have been conducted from the perspective of inflammation. Here, we hypothesized that a non-inflammatory factor induces lacrimal hyposecretion in SS pathology, and to elucidate such a factor, we conducted transcriptome analysis of the lacrimal glands in male non-obese diabetic (NOD) mice as an SS model. The NOD mice showed inflammatory cell infiltration and decreased pilocarpine-induced tear secretion at and after 6 weeks of age compared to age-matched BALB/c mice. RNA-sequencing analysis revealed that only four genes, including arginase 1, were downregulated, whereas many genes relating to inflammation were upregulated, in the lacrimal glands of male NOD mice after onset of lacrimal hyposecretion and dacryoadenitis (lacrimal gland inflammation). Changes in the level of arginase 1 expression were confirmed by real-time RT-PCR and western blot analysis. Furthermore, non-dacryoadenitis-type NOD mice were used to investigate the relationships among arginase 1 expression, lacrimal hyposecretion and dacryoadenitis. Interestingly, these NOD mice retained the phenotype of dacryoadenitis with regard to tear secretion and arginase 1 expression level. An arginase 1 inhibitor reduced tear secretion and partially reduced saliva secretion in BALB/c mice. In conclusion, a non-inflammatory factor, arginase 1, is involved in lacrimal hyposecretion in male NOD mice, regardless of dacryoadenitis status. These results shed light on the pathophysiological role of arginase 1 in SS (dry eye).
32387470 COVID-19 gone bad: A new character in the spectrum of the hyperferritinemic syndrome? 2020 Jul The severe form of COVID-19 share several clinical and laboratory features with four entities gathered under the term "hyperferritinemic syndromes" and including macrophage activation syndrome (MAS), adult-onset Still's disease (AOSD), catastrophic anti-phospholipid syndrome (CAPS) and septic shock. COVID-19 systemic inflammatory reaction and "hyperferritinemic syndromes" are all characterized by high serum ferritin and a life-threatening hyper-inflammation sustained by a cytokines storm which eventually leads to multi-organ failure. In this review, we analyze the possible epidemiological and molecular mechanisms responsible for hyper-inflammation in patients with severe COVID-19 and we underline the similarities between this condition and "hyperferritinemic syndromes" which would allow considering severe COVID-19 as a fifth member of this spectrum of inflammatory conditions.
32330965 Congenital Complete Atrioventricular Heart Block in a Pregnant Woman with Sjögren Syndrom 2020 Apr The present report describes a case of complete atrioventricular block (CAVB) diagnosed at 25 weeks of gestation in a pregnant woman with Sjögren's syndrome and positive anti-Ro/SSA antibodies. Fluorinated steroids (dexamethasone and betamethasone) and terbuline were used to increase the fetal heart rate, but the fetal heart block was not reversible, and the administration of drugs was discontinued due to maternal collateral effects. Follow-up fetal echocardiograms were performed, and the fetus evolved with pericardial effusion, presence of fibroelastosis in the right ventricle, and ventricular dysfunction. Interruption of pregnancy by cesarean section was indicated at 34 weeks of gestation, and a cardiac pacemaker was implanted in the male newborn immediately after birth. Therapy for fetuses with CAVB is controversial mainly regarding the use or not of corticosteroids; however, monitoring of the atrioventricular interval by fetal echocardiography should be performed in fetuses from pregnant women with positive autoantibodies anti-Ro/SSA and/or anti-La/SSB to prevent the progression to CAVB.
31302686 Risk of Wnt/β-catenin signalling pathway gene polymorphisms in primary Sjögren's syndrom 2020 Feb 1 OBJECTIVE: To explore genetic polymorphisms of the Wnt/β-catenin signalling pathway in primary SS (PSS). METHODS: We included 98 patients with PSS and 165 healthy volunteers. Genomic DNA was extracted from peripheral blood samples. Through an open-array platform of low density, we genotyped 25 polymorphisms from 14 genes (WISP1, DKK1, SOST, FRZB, LRP1, LRP4, LRP5, LRP6, GSKB, ADAMTS5, GDF5, FMN2, ADIPOQ and COL11A1) involved in the Wnt/β-catenin signalling pathway. We compared the allelic and genotypic frequencies with Fisher's exact test and logistic regression analysis adjusted by age, gender and individual admixture, as well as bootstrap-resampling analysis. We assessed the gene-gene interaction by the multifactor dimensionality reduction method. RESULTS: We found a positive significant association with four polymorphisms: LRP5 rs606989, FRZB rs409238, GSK3B rs2037547 and ADIPOQ rs2241766. All of them conferred risk for PSS, being the highest among subjects carrying three to four risk alleles (P < 0.001). According to a multifactor dimensionality reduction analysis, the best models included the LRP5 (rs606989), FRZB (rs409238) and ADIPOQ (rs2241766) polymorphisms. CONCLUSION: LRP5, FRZB and ADIPOQ genes related in the Wnt/β-catenin signalling pathway increased the risk of PSS. Further research is needed to establish their functional role in this clinical entity.
32107824 Environmental factors in the pathogenesis of primary Sjögren's syndrome. 2020 May Primary Sjögren's syndrome (SS) is a systemic autoimmune disease in which exocrine organs, primarily the salivary and lacrimal glands, are targets of chronic inflammation, leading to severe dryness of eyes and mouth. Fatigue and arthralgia are also common, and extraglandular manifestations involving the respiratory, nervous and vascular systems occur in a subset of patients. Persistent activation of the type I interferon system, and autoreactive B and T cells with production of disease-associated autoantibodies are central to the pathogenesis. Genetic polymorphisms that associate with an increased risk of SS have been described, though the risk-increase contributed by the respective variant is generally low. It is thus becoming increasingly clear that genetics cannot alone account for the development of SS and that other, presumably exogenous, factors must play a critical role. Relatively few studies have investigated exposure to potential risk factors prior to SS disease onset. Rather, many factors have been studied in prevalent cases. In this review, we summarize current literature on exogenous factors in the pathogenesis of SS including infections, hormones, smoking, solvents and additional compounds. We delineate for which factors there is current evidence of increased disease risk, and for which our present knowledge is confined to suggesting their role in SS pathogenesis. Finally, we outline future perspectives in the continued search for environmental risk factors for SS, a research area of great importance considering the possibilities for preventive measures.
31957508 Canakinumab for the treatment of adult-onset Still's disease. 2020 Feb Introduction: Adult-onset Still's disease (AOSD) is a rare multisystem autoinflammatory disorder of unknown etiology, with clinical and biological similarities with the juvenile form (sJIA).The pivotal role of interleukin (IL)-1 gives rise to the use of IL-1 inhibitors in treating resistant cases.Areas covered: This review focuses on canakinumab, a fully human anti-IL-1β antibody, as treatment for AOSD. The data obtained from case reports and case series on AOSD and two double-blind, randomized, placebo-controlled Phase III trial on sJIA are analyzed. Efficacy and safety profiles of canakinumab are discussed.Expert opinion: There is no unanimous consensus on how to treat with IL-1 inhibitors. Many reviews have focused primarily on anakinra, but the accumulating data for canakinumab have emerged. The choice of treatment is a relevant issue for patients and the national health services. The available data for canakinumab indicate that this drug in AOSD patients is effective and well tolerated.
32386116 Probiotic Use and Psoriatic Arthritis Disease Activity. 2020 Jun OBJECTIVE: Probiotics have been hypothesized to mediate inflammation through gut microbiome modulation. Spondyloarthropathies have subclinical gut inflammation associated with inflammatory disease that may benefit from probiotic use. We aimed to evaluate associations between probiotic use and patient-reported outcomes in patients with psoriatic arthritis (PsA). METHODS: Using FORWARD, The National Databank for Rheumatic Diseases, we examined probiotic use among patients with PsA and rheumatoid arthritis (RA), a comparator in which gut inflammation is less clearly related to pathogenesis. Patient-reported outcome measures such as pain and physical function were compared for probiotic users and nonusers among patients with PsA and RA. Patients were propensity score-matched for taking a probiotic by demographics and nonmedication supplements. RESULTS: More patients have reported probiotic use over the past decade, with less than 1% reporting use in 2008 and approximately 7% in 2018. Probiotic users are more likely to be white women with higher education, income, and supplement use. Following propensity score matching, probiotic users with PsA had significantly lower Short Form 36 Physical Component Summary (SF-36 PCS) scores and higher pain scores than nonusers with PsA (33.11 ± 11.50 vs. 40.82 ± 11.03; P = 0.04 and 4.78 ± 3.09 vs. 3.00 ± 2.58; P = 0.03). There were no significant differences in Patient Activity Scale II, Health Assessment Questionnaire II, SF-36 PCS, and Short Form 36 Mental Component Summary scores or pain among users with PsA before and after probiotic initiation. CONCLUSION: We found increasing probiotic use in patients with PsA and important differences between users and nonusers. After accounting for these differences, we found no statistical difference in health outcomes after probiotic use.
31540835 [Drug-induced Sweet's syndrome related to hydroxychloroquine: About 2 cases]. 2020 Apr INTRODUCTION: Hydroxychloroquine is widely prescribed in systemic lupus erythematosus. Dermatologic adverse drug reactions are rare but can mimic a disease specific manifestation of lupus. Exceptionally, Sweet's syndrome, or acute febrile neutrophilic dermatosis, may be drug-induced. CASE REPORTS: Two patients aged 31 and 42 years were treated with hydroxychloroquine for systemic lupus and Sjogren's syndrome, respectively. Three weeks after starting treatment, they had a febrile, purple and erythematous papular rash of the trunk and limbs. There was a biological inflammatory syndrome and skin biopsy disclosed an infiltrate of the dermis rich in neutrophils. Lesions regressed after stopping hydroxychloroquine and introducing systemic corticosteroid therapy. Allergologic tests discussed the differential diagnosis with a delayed-type hypersensitivity reaction. CONCLUSION: We report two exceptional cases of drug-induced Sweet's syndrome related to hydroxychloroquine treatment in autoimmune rheumatic diseases.
32847874 Adjuvant rituximab improves sensory ataxia in CIDP-related Sjögren syndrome. 2020 Aug 26 Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune neuropathy characterised by insidious onset, progressive course, proximal and distal symmetrical weakness, and sensory impairment. It may affect patients of any age with varying degrees of clinical involvement and response rates to existing treatments. Sjögren syndrome (SS) is a systemic autoimmune disorder that primarily affects the exocrine glands causing a sicca syndrome. It may affect the peripheral nervous system, usually causing painful small fibre or pure sensory axonal neuropathy, ganglioneuronopathy or a predominantly sensory CIDP. We report the case of a 71-year-old man diagnosed with a debilitating and difficult-to-treat CIDP who, 5 years later, developed SS with pulmonary involvement. Due to lack of response to treatments other than periodic intravenous immunoglobulin (IVIg) every 12 days, we started adjuvant treatment with rituximab which increased the time interval between IVIg therapies by 50%, providing better quality of life for the patient.
31420813 Effectiveness and safety of abatacept for the treatment of patients with primary Sjögren' 2020 Jan Sjögren's syndrome is an autoimmune disease characterized by inflammation of the exocrine glands. The disease can be primary or secondary (if it is associated with another autoimmune disease). In Barring symptom management, there is no established treatment. To evaluate the effectiveness and safety of abatacept as a treatment of primary Sjögren's syndrome over the course of 24 months. Eleven patients with primary Sjögren's syndrome from the Rheumatology Department of Universidade Santo Amaro, Sao Paulo, Brazil were enrolled for a prospective observational study. Eligible participants were diagnosed according to the 2002 American-European consensus criteria and had a score greater than 3 on the EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI). Participants received intravenous abatacept for 24 months at a weight-adjusted dose of 500 mg for patients weighing < 60 kg and 750 mg for those weighing > 60 kg. The outcomes were ESSDAI activity index, non-stimulated salivary flow rate, ocular dryness (Schirmer test, tear film break-up time, and ocular staining score), SF-36 questionnaire, and Fatigue domain of the FACIT (Functional Assessment of Chronic Illness Therapy) index. There was a statistically significant reduction in ESSDAI index and improvement of salivary flow. One subscale of the SF-36 index-emotional role functioning-showed improvement. There was no change in ocular parameters or in the FACIT index. In this sample of 11 patients with primary Sjögren's syndrome, abatacept therapy improved xerostomia and systemic disease activity.Key Points• Abatacept is safe and effective for the treatment of primary Sjögren's syndrome.• Abatacept can improve salivary flow and ESSDAI index in this patient population.
31329136 Radiomics-Based Assessment of Primary Sjögren's Syndrome From Salivary Gland Ultrasonogra 2020 Mar Salivary gland ultrasonography (SGUS) has shown good potential in the diagnosis of primary Sjögren's syndrome (pSS). However, a series of international studies have reported needs for improvements of the existing pSS scoring procedures in terms of inter/intra observer reliability before being established as standardized diagnostic tools. The present study aims to solve this problem by employing radiomics features and artificial intelligence (AI) algorithms to make the pSS scoring more objective and faster compared to human expert scoring. The assessment of AI algorithms was performed on a two-centric cohort, which included 600 SGUS images (150 patients) annotated using the original SGUS scoring system proposed in 1992 for pSS. For each image, we extracted 907 histogram-based and descriptive statistics features from segmented salivary glands. Optimal feature subsets were found using the genetic algorithm based wrapper approach. Among the considered algorithms (seven classifiers and five regressors), the best preforming was the multilayer perceptron (MLP) classifier (κ = 0.7). The MLP over-performed average score achieved by the clinicians (κ = 0.67) by the considerable margin, whereas its reliability was on the level of human intra-observer variability (κ = 0.71). The presented findings indicate that the continuously increasing HarmonicSS cohort will enable further advancements in AI-based pSS scoring methods by SGUS. In turn, this may establish SGUS as an effective noninvasive pSS diagnostic tool, with the final goal to supplement current diagnostic tests.
29754950 Oral health-related quality of life in primary Sjögren's syndrome. 2020 Mar OBJECTIVE: To assess health-related quality of life (HRQoL) and oral health-related quality of life, and correlate them with unstimulated whole salivary flow (UWSF) and oral sicca symptoms in patients with primary Sjögren's syndrome (PSS). METHODS: We included 60 patients with PSS and 60 healthy controls matched according to gender and age (±3 years). We measured the UWSF and scored the European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI). We assessed the short version of the SF-36 as a generic measurement of HRQoL and the Xerostomia Quality of Life Scale (XeQoLS) questionnaire to evaluate oral quality of life. We evaluated oral symptoms using an 8-item Visual Analogue Scale (VAS) questionnaire. RESULTS: We observed a poorer HRQoL (lower scores in SF-36) and oral quality of life (higher scores in XeQoLS), as well as a greater severity of symptoms in the VAS questionnaire upon comparing patients vs. controls. The XeQoL correlated with the UWSF (τ = -0.24, P = .008), the ESSPRI (τ =0.45, P = .0001), VAS 1-2 and VAS 5-8 and the SF-36 score (τ = -0.28, P = .002). CONCLUSIONS: Patients with PSS had a poorer HRQoL and oral quality of life than controls. UWSF contributes to the oral quality of life which, in turn, has an impact on HRQoL. Symptomatic treatment of xerostomia as well as the prevention of infections, decay and tooth loss would help to improve the oral quality of life in these patients.
34513612 Clinical Pharmacology Aspects in Patients Treated with TNF Inhibitors During SARS-Cov-2 Pa 2021 May In this period of global pandemic caused by SARS-Cov-2, it is of paramount importance to recognize all risk factors that may increase the likelihood of infection. In addition to the risk factors known as pre-existing diseases and old age, risk factors could be drug treatments for chronic diseases, such as immunomodulating drugs that can alter immune defences and response to infectious agents. Antibodies that inhibit tumor necrosis factor (TNF) such as adalimumab infliximab etanercept and golimumab have been used for over 20 years in severe cases of autoimmune diseases such as rheumatoid arthritis, inflammatory bowel disease or ankylosing spondylitis. Due to their mechanism of action they reduce inflammation and can stop the progression of the disease by inhibiting a key factor of inflammation such as TNF. In this article we want to examine the possible correlation between therapy with TNF inhibitors and the increased risk of SARS-CoV-2 infection, and the possible paradoxical therapeutic efficacy in patients with ongoing infection, especially in phase two and three. We express our opinion on this very complex and sensitive topic which is the subject of discussion among physicians and experts, based on current knowledge of the literature.
33042817 Polymeric Nanoscale Drug Carriers Mediate the Delivery of Methotrexate for Developing Ther 2020 Methotrexate (MTX) is widely used as an anticancer and anti-inflammtory drug for treating various types of cancer and autoimmune diseases. The optimal dose of MTX is known to inhibit the dihydrofolatereductase that hinders the replication of purines. The nanobiomedicine has been extensively explored in the past decade to develop myriad functional nanostructures to facilitate the delivery of therapeutic agents for various medical applications. This review is focused on understanding the design and development of MTX-loaded nanoparticles alongside the inclusion of recent findings for the treatment of cancers. In this paper, we have made a coordinated effort to show the potential of novel drug delivery systems by achieving effective and target-specific delivery of methotrexate.
32973552 The NLRP3 Inflammasome: Role and Therapeutic Potential in Pain Treatment. 2020 Pain is a fundamental feature of inflammation. The immune system plays a critical role in the activation of sensory neurons and there is increasing evidence of neuro-inflammatory mechanisms contributing to painful pathologies. The inflammasomes are signaling multiprotein complexes that are key components of the innate immune system. They are intimately involved in inflammatory responses and their activation leads to production of inflammatory cytokines that in turn can affect sensory neuron function. Accordingly, the contribution of inflammasome activation to pain signaling has attracted considerable attention in recent years. NLRP3 is the best characterized inflammasome and there is emerging evidence of its role in a variety of inflammatory pain conditions. In vitro and in vivo studies have reported the activation and upregulation of NLRP3 in painful conditions including gout and rheumatoid arthritis, while inhibition of NLRP3 function or expression can mediate analgesia. In this review, we discuss painful conditions in which NLRP3 inflammasome signaling has been pathophysiologically implicated, as well as NLRP3 inflammasome-mediated mechanisms and signaling pathways that may lead to the activation of sensory neurons.
32801046 Update on IgG4-mediated autoimmune diseases: New insights and new family members. 2020 Oct Antibodies of IgG4 subclass are exceptional players of the immune system, as they are considered to be immunologically inert and functionally monovalent, and as such may be part of classical tolerance mechanisms. IgG4 antibodies are found in a range of different diseases, including IgG4-related diseases, allergy, cancer, rheumatoid arthritis, helminth infection and IgG4 autoimmune diseases, where they may be pathogenic or protective. IgG4 autoimmune diseases are an emerging new group of diseases that are characterized by pathogenic, antigen-specific autoantibodies of IgG4 subclass, such as MuSK myasthenia gravis, pemphigus vulgaris and thrombotic thrombocytopenic purpura. The list of IgG4 autoantigens is rapidly growing and to date contains 29 candidate antigens. Interestingly, IgG4 autoimmune diseases are restricted to four distinct organs: 1) the central and peripheral nervous system, 2) the kidney, 3) the skin and mucous membranes and 4) the vascular system and soluble antigens in the blood circulation. The pathogenicity of IgG4 can be validated using our classification system, and is usually excerted by functional blocking of protein-protein interaction.
32699627 A patient with chronic kidney disease, primary biliary cirrhosis and metabolic acidosis. 2020 Jun Autoimmune disorders such as rheumatoid arthritis or Sjögren's syndrome can be associated with impaired renal acid excretion. Only few cases of patients with primary biliary cirrhosis (PBC) and distal renal tubular acidosis (dRTA) have been described. Here, we present the case of a 60-year-old woman with PBC and dRTA. Her kidney biopsy showed an absence of markers of acid-secretory Type A intercalated cells (A-ICs) and expression of aquaporin-2, a marker of principal cells, in all cells lining the collecting duct. Moreover, the serum of the patient contained antibodies directed against a subset of cells of the collecting duct. Thus, PBC-related autoantibodies may target acid-secretory A-ICs and thereby impair urinary acidification.