Management of liver disease and portal hypertension in cystic fibrosis: a review.

INTRODUCTION: Cystic fibrosis (CF)-associated liver disease can significantly affect the quality of life and survival of people with CF. The hepatobiliary manifestations in CF are various, with focal/multilobular biliary cirrhosis more common in children and porto-sinusoidal vascular disease (PSVD) in young adults. Portal hypertensive complications, particularly bleeding from esophagogastric varices and hypersplenism are common, while liver failure is rarer and mainly linked to biliary disease. AREAS COVERED: This review explores current therapeutic options for CF-associated liver disease, presenting ongoing studies and new insights into parthenogenesis for potential future therapies. EXPERT OPINION: Monitoring for signs of portal hypertension is essential. Limited evidence supports ursodeoxycholic acid (UDCA) efficacy in halting CF liver disease progression. The effect of cystic fibrosis transmembrane conductance regulator (CFTR) modulators on liver outcomes lacks definitive data, since patients with CF-related liver disease were excluded from trials due to potential hepatotoxicity. A proposed approach involves using UDCA and modulators in early stages, along with anti-inflammatory agents, with further therapeutic strategies awaiting randomized trials. Prevention of portal hypertensive bleeding includes endoscopic sclerotherapy or ligation of esophageal varices. Nonselective beta-blockers may also prevent bleeding and could be cautiously implemented. Other non-etiological treatments require investigation.

Glomerulonephritis in primary biliary cholangitis in China: an important complication.

BACKGROUND: Extrahepatic manifestations in patients with primary biliary cholangitis (PBC) are frequently observed recently. We aimed in this study to explore the clinicopathological characteristics and prognosis of glomerulonephritis in patients with PBC. METHODS: Consecutive PBC patients admitted to Peking Union Medical College Hospital from January 2002 to May 2019 were retrospectively enrolled. PBC patients with other autoimmune diseases which may have nephritis were excluded. Structured interview, systemic rheumatologic examination, and laboratory tests were conducted for each patient. Literature about patients with PBC and glomerulonephritis was reviewed and summarized. RESULTS: Among the 330 PBC patients enrolled, glomerulonephritis were identified in 10 patients (3.0%). Eight (80.0%) were females and 2 (20.0%) were males. The mean age was 58.4 ± 9.5 years old. Membranous nephropathy (MN) was revealed in 4 patients, IgA nephropathy (IgA N) in 2 patients, minimal change disease (MCD) in 2 patients, mesangial proliferative glomerulonephritis in 1 patient, and renal amyloidosis in 1 patient. Compared to the literature reviewed, 10 cases of MN, 1 case of MCD, 1 case of IgA N, and 1 case of acute poststreptococcal glomerulonephritis (APSGN) were observed. CONCLUSIONS: Glomerulonephritis may not be a well-recognized feature of PBC and is not a rare complication and deserved to be routinely screened in clinical practice. As MN is the most common form of glomerulonephritis in PBC patients and PBC can be asymptomatic at an early stage, patients presented with MN should be screened for PBC, so to avoid cirrhosis. Key Points • Patients with primary biliary cholangitis (PBC) can be complicated with glomerulonephritis, and membranous nephropathy (MN) is the most common form.

Autoimmune Liver Diseases and Rheumatoid Arthritis-Is There an Etiopathogenic Link?

Rheumatoid arthritis (RA) is a systemic immune-mediated disease that, in addition to the articular involvement, can have extra-articular manifestations. Even though liver damage in RA is not very common, associated autoimmune liver diseases (AILDs) may occur. The most common AILD associated with RA is primary biliary cirrhosis (PBC), followed by autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC). There are common underlying mechanisms that play a role in the emergence of autoimmunity and inflammation in both rheumatic and autoimmune liver diseases. Genetic studies have revealed the existence of several common disease-associated genes shared between RA and AILDs, and infectious triggers, particularly those associated with recurrent or complicated urinary tract infections, are also speculated to be potential triggers for these conditions. Moreover, these diseases share common serologic patterns characterized by the presence of specific autoantibodies and hyper-gammaglobulinemia. In this study, we focus on reviewing the association between RA and AILDs regarding the prevalence and possible etiopathogenic link.

Unprecedented complexity of six coexisting autoimmune diseases: A case report.

INTRODUCTION: Autoimmune disorders often exhibit interconnectedness, although encountering multiple autoimmune conditions in a single patient is uncommon. Multiple autoimmune syndrome is characterized by the presence of at least three distinct autoimmune diseases in an individual. This report outlines the case of a middle-aged woman diagnosed with autoimmune thyroiditis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, and antisynthetase syndrome. Additionally, it includes a literature review encompassing multiple autoimmune syndromes involving five or more autoimmune diseases. OBSERVATION: A 57-year-old woman, with no previous medical history, presented with fever, extensive muscle weakness, progressive exertional dyspnea, inflammatory polyarthralgia, dysphagia, and dry mouth. Clinical examination revealed muscular deficit in the scapular and pelvic girdles, distal muscular deficit, synovitis in the wrists, and features indicative of "mechanic's hand". Laboratory examinations showed cytolysis, cholestasis, elevated muscle enzymes, hypergammaglobulinemia and elevated thyroid stimulating hormone. Immunoassays showed positive results for antinuclear antibodies, anti-histidyl-t-RNA synthetase, anti-Sjögren's-syndrome-related antigen A, anti-ribonucleic-acid-polymerase-III-RP155, anti-fibrillarin, anti-mitochondrial, anti-liver/kidney microsomal type 1, anti-glycoprotein 210, and anti-thyroid peroxidase antibodies. Further investigations led to the diagnosis of a multiple autoimmune syndrome involving autoimmune thyroiditis, Sjögren's syndrome, scleroderma, autoimmune hepatitis, primary biliary cirrhosis, and antisynthetase syndrome. The patient received treatment with intravenous immunoglobulins, corticosteroids, azathioprine, and ursodeoxycholic acid, which resulted in favorable clinical and biological outcomes. CONCLUSION: This patient presented with six concurrent distinct autoimmune disorders, categorizing this case as a type two multiple autoimmune syndrome. The identification of antisynthetase syndrome notably distinguishes this case.

Patented Farnesoid X receptor modulators: a review (2019 - present).

INTRODUCTION: The Farnesoid X receptor (FXR) is a key transcription factor that is involved in the bile acid signaling network. The modulation of the FXR activity influences glucose and lipid homeostasis, reduces obesity and insulin resistance, as well as it regulates the pathogenesis of inflammatory and metabolic disorders. FXR ligands have therefore emerged in drug discovery as promising therapeutic agents for the prevention and treatment of gastrointestinal and liver diseases, including cancer. AREAS COVERED: Recent advances in the field of FXR modulators are reviewed, with a particular attention on patent applications filed in the past 5 years related to both the discovery and development of FXR targeting drugs. EXPERT OPINION: FXR agonists have proven their efficacy and safety in humans and have shown a significant potential as clinical agents to treat metabolic and inflammatory associated conditions. However, several challenges, including adverse events such as pruritus, remain to be solved. Current studies aim to gain insights into the pathophysiological mechanisms by which FXR regulates metabolism and inflammation in terms of tissue/organ/isoform-specificity, post-translational modifications and coregulatory proteins, on the route of novel, improved FXR modulators.

Primary biliary cholangitis presenting with granulomatous lung disease misdiagnosed as lung cancer: A case report.

BACKGROUND: There are few cases of pulmonary granulomatous changes secondary to primary biliary cirrhosis (PBC). No case of granulomatous lung disease secondary to PBC misdiagnosed as lung cancer had been reported. CASE SUMMARY: A middle-aged woman presented with lung nodules and was misdiagnosed with lung cancer by positron emission tomography/computed tomography. She underwent left lobectomy, and the pathology of the nodules showed granulomatous inflammation, which was then treated with antibiotics. However, a new nodule appeared. Further investigation with lung biopsy and liver serology led to the diagnosis of PBC, and chest computed tomography indicated significant reduction in the pulmonary nodule by treatment with methylprednisolone and ursodeoxycholic acid. CONCLUSION: Diagnosis of pulmonary nodules requires integrating various clinical data to avoid unnecessary pulmonary lobectomy.

Add-on immunosuppressive therapy may benefit selected patients with primary biliary cholangitis and autoimmune phenomena.

Background: Mildly elevated levels of transaminase and/or immunoglobulin G (IgG) are common in patients with primary biliary cholangitis (PBC). It is still unclear whether adding immunosuppressive therapy to ursodeoxycholic acid (UDCA) benefits those patients who are not fulfilling the diagnostic criteria of PBC with autoimmune hepatitis (AIH) features. Objectives: To assess the efficacy of adding immunosuppressive therapy to UDCA for patients with PBC and autoimmune phenomena but not fulfilling the diagnostic criteria of PBC with AIH features. Design: This is a retrospective-prospective cohort study in a tertiary medical center. Methods: Patients with PBC and autoimmune phenomena were defined by the elevation of IgG and/or transaminase but did not fulfill the diagnostic criteria of PBC with AIH features. We grouped these patients based on with and without add-on immunosuppressive therapy and balanced their baseline characteristics using inverse probability treatment weighting (IPTW). Results: A total of 652 patients with PBC and autoimmune phenomena were included, with a median follow-up of 4.08 years. After IPTW, the pseudo sample size in the add-on therapy and monotherapy groups was 558 and 655, respectively. After 1 year of observation, patients in the add-on therapy group had a higher biochemical response rate (normalization of transaminase and IgG levels) (49% versus 17%, p < 0.001). Furthermore, add-on therapy improved the transplant-free survival in the subgroup of patients with PBC and transaminase ⩾3 × upper limit of normal (ULN) or IgG ⩾1.3 × ULN (p = 0.033). Conclusion: Add-on immunosuppressive therapy may improve the normalization rates of transaminase and IgG levels in all patients with PBC and mildly elevated transaminase and IgG levels and the long-term outcomes in the subgroup of the patients with transaminase ⩾3 × ULN or IgG ⩾1.3 × ULN.

A look at add-on immunosuppressive therapy in primary biliary cholangitis patients Adding immunosuppressive therapy may enhance the normalization of ALT, AST and IgG levels in all PBC patients with mild elevation and improve long-term outcomes in those with more severe elevation of ALT, AST and IgG. These findings contribute to our understanding of treatment options for PBC patients with autoimmune phenomena.

Liver cirrhosis requiring transplantation in the context of hepaticojejunostomy stricture after a traumatic bile duct injury.

Biliary injury secondary to trauma is frequently associated with long-term complications. Liver transplantation is rarely indicated but might be the best therapeutic option in severe or intractable cases. We report the case of a 19-year-old male referred for liver transplantation due to biliary injury after abdominal trauma. A Roux-en-Y hepaticojejunostomy was initially performed without immediate complications. Anastomotic stricture developed requiring several trials of biliary dilatation and stenting through a percutaneous approach. The presence of liver cirrhosis and the intractability of this complication culminated in the decision of liver transplantation. The authors present clinical course, complications and interventional procedures that were used in a judicious step-up approach.

Causal relationship between systemic lupus erythematosus and primary liver cirrhosis based on two-sample bidirectional Mendelian randomization and transcriptome overlap analysis.

BACKGROUND: Overlapping cases of systemic lupus erythematosus (SLE) and primary biliary cirrhosis (PBC) are rare and have not yet been fully proven to be accidental or have a common genetic basis. METHODS: Two-sample bidirectional Mendelian randomization (MR) analysis was applied to explore the potential causal relationship between SLE and PBC. The heterogeneity and reliability of MR analysis were evaluated through Cochran's Q-test and sensitivity test, respectively. Next, transcriptome overlap analysis of SLE and PBC was performed using the Gene Expression Omnibus database to identify the potential mechanism of hub genes. Finally, based on MR analysis, the potential causal relationship between hub genes and SLE or PBC was validated again. RESULTS: The MR analysis results indicated that SLE and PBC were both high-risk factors for the occurrence and development of the other party. On the one hand, MR analysis had heterogeneity, and on the other hand, it also had robustness. Nine hub genes were identified through transcriptome overlap analysis, and machine learning algorithms were used to verify their high recognition efficiency for SLE patients. Finally, based on MR analysis, it was verified that there was no potential causal relationship between the central gene SOCS3 and SLE, but it was a high-risk factor for the potential risk of PBC. CONCLUSION: The two-sample bidirectional MR analysis revealed that SLE and PBC were high-risk factors for each other, indicating that they had similar genetic bases, which could to some extent overcome the limitation of insufficient overlap in case samples of SLE and PBC. The analysis of transcriptome overlapping hub genes provided a theoretical basis for the potential mechanisms and therapeutic targets of SLE with PBC overlapping cases.

Noninvasive prediction of insufficient biochemical response after ursodeoxycholic acid treatment in patients with primary biliary cholangitis based on pretreatment nonenhanced MRI.

OBJECTIVES: To explore the feasibility of pretreatment nonenhanced magnetic resonance imaging (MRI) in predicting insufficient biochemical response to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC). METHODS: From January 2009 to April 2022, consecutive PBC patients who were treated with UDCA and underwent nonenhanced MRI within 30 days before treatment were retrospectively enrolled. All MR images were independently evaluated by two blinded radiologists. Uni- and multivariable logistic regression analyses were performed to develop a predictive model for 12-month insufficient biochemical response. Model performances were evaluated by computing the area under the receiver operating characteristic curve (AUC), sensitivity, and specificity. RESULTS: A total of 74 patients (50.6 ± 11.9 years; 62 females) were included. Three pretreatment MRI features, including hepatomegaly (odds ratio [OR]: 4.580; p = 0.011), periportal hyperintensity on T2-weighted imaging (T2WI) (OR: 4.795, p = 0.008), and narrowing of the bile ducts (OR: 3.491; p = 0.027) were associated with 12-month insufficient biochemical response in the multivariable analysis. A predictive model based on the above indicators had an AUC of 0.781, sensitivity of 85.4%, and specificity of 61.5% for predicting insufficient biochemical response. CONCLUSIONS: A noninvasive model based on three pretreatment MRI features could accurately predict 12-month insufficient biochemical response to UDCA in patients with PBC. Early identification of PBC patients at increased risk for insufficient response can facilitate the timely initiation of additional treatment. CLINICAL RELEVANCE STATEMENT: A noninvasive predictive model constructed by incorporating three pretreatment MRI features may help identify patients with primary biliary cholangitis at high risk of insufficient biochemical response to ursodeoxycholic acid and facilitate the timely initiation of additional treatment. KEY POINTS: • Noninvasive imaging features based on nonenhanced pretreatment MRI may predict an insufficient biochemical response to UDCA in PBC patients. • A combined model based on three MRI features (hepatomegaly, periportal hyperintensity on T2-weighted imaging, and narrowing of the bile ducts) further improved the predictive efficacy for an insufficient biochemical response to UDCA in PBC patients, with high sensitivity and specificity. • The nomogram of the combined model showed good calibration and predictive efficacy for an insufficient biochemical response to UDCA in PBC patients. In particular, the calibration curve visualised the clinical applicability of the prediction model.

[Suspected autoimmune coagulation factor IX deficiency difficult to diagnose due to concurrent lupus anticoagulant].

A woman in her 70s who was undergoing treatment for an overlap syndrome of autoimmune hepatitis and primary biliary cirrhosis developed persistent genital bleeding. Coagulation tests revealed a longer activated partial thromboplastin time, a 7% decrease in coagulation factor IX activity (FIX:C) and a FIX inhibitor (of 3 BU/ml). Lupus anticoagulant (LA), anticardiolipin antibody, and anti-ß2 glycoprotein I antibody were positive, and the activated partial thromboplastin time cross-mixing test suggested the presence of LA. Additionally, all intrinsic coagulation factors decreased, but activity of all factors except FIX showed dilution linearity, which suggested a false decrease in activity due to LA. Although definitive diagnosis was difficult due to concurrent LA, this case was strongly suspected to be autoimmune coagulation FIX deficiency complicated by LA. Bypass therapy was not performed because the patient had no anemia and was positive for LA, and immunosuppressive therapy with prednisolone was initiated immediately. Eleven weeks after diagnosis, FIX:C was 41% and zFIX inhibitor was less than 1 BU/ml, leading to remission.

The causality between gut microbiome and liver cirrhosis: a bi-directional two-sample Mendelian randomization analysis.

Background and aim: Previous studies have reported an association between gut microbiota and cirrhosis. However, the causality between intestinal flora and liver cirrhosis still remains unclear. In this study, bi-directional Mendelian randomization (MR) analysis was used to ascertain the potential causal effect between gut microbes and cirrhosis. Methods: Large-scale Genome Wide Association Study (GWAS) data of cirrhosis and gut microbes were obtained from FinnGen, Mibiogen consortium, and a GWAS meta-analysis of Alcoholic cirrhosis (ALC). Two-sample MR was performed to determine the causal relationship between gut microbiota and cirrhosis. Furthermore, a bi-directional MR analysis was employed to examine the direction of the causal relations. Result: In MR analysis, we found that 21 gut microbiotas were potentially associated with cirrhosis. In reverse MR analysis, 11 gut microbiotas displayed potentially associations between genetic liability in the gut microbiome and cirrhosis. We found that the family Lachnospiraceae (OR: 1.59, 95% CI:1.10-2.29) might be harmful in cirrhotic conditions (ICD-10: K74). Furthermore, the genus Erysipelatoclostridium might be a protective factor for cirrhosis (OR:0.55, 95% CI:0.34-0.88) and PBC (OR:0.68, 95% CI:0.52-0.89). Combining the results from the MR analysis and reverse MR analysis, we firstly identified the Genus Butyricicoccus had a bi-directional causal effect on PBC (Forward: OR: 0.37, 95% CI:0.15-0.93; Reverse: OR: 1.03, 95% CI:1.00-1.05). Conclusion: We found a new potential causal effect between cirrhosis and intestinal flora and provided new insights into the role of gut microbiota in the pathological progression of liver cirrhosis.

Antimitochondrial antibody-negative primary biliary cirrhosis with secondary Sjogren syndrome: a case report.

Introduction and importance: Primary biliary cholangitis (PBC) is a rare immune-mediated liver disease characterized by the destruction of intrahepatic bile ducts and a positive antimitochondrial antibody (AMA), which is considered a serological hallmark for the diagnosis. Rarely, AMA can be absent/nondetectable in a few cases and is referred to as 'AMA-negative'. Case presentation: The authors present such an uncommon case of AMA-negative PBC in a 39-year-female with Sjogren's syndrome who presented with fatigue, pruritus, and dry eyes. Clinical discussion: Previously published studies state that approximately only about 5% of patients with PBC are 'AMA-negative'. For patients negative for AMA, the diagnosis has to be based on typical pathological features of this disease. Once a diagnosis of PBC is established, regardless of whether it is positive or negative for AMAs, ursodeoxycholic acid is a widely accepted treatment. Conclusion: The presence/absence of AMAs is associated with similar clinical, biochemical, and histopathological characteristics in PBC. The identification of AMAs alone should not impact the diagnosis or treatment of PBC.

Spleen Thickness Plus Platelets Can Effectively and Safely Screen for High-Risk Varices in Cirrhosis Patients.

Currently, most primary hospitals cannot routinely perform liver stiffness measurements (LSMs) and spleen stiffness measurements (SSMs), which are recommended by guidelines to exclude high-risk varices (HRVs). We tried to find more convenient indicators for HRV screening. We enrolled 213 cirrhosis patients as the training cohort (TC) and 65 primary biliary cirrhosis patients as the validation cohort (VC). We included indicators such as SSM by two-dimensional shear wave elastography, LSM by transient elastography, and other imaging and laboratory tests. Variable analysis revealed SSM, platelets (PLT), and spleen thickness (ST) as independent risk indicators for HRV. In TC, ST+PLT (ST < 42.2 mm and PLT > 113.5 × 109/L) could avoid 35.7% of the esophagogastroduodenoscopies (EGDs), with a 2.4% missed HRV rate. Although the proportion of EGDs spared by ST+PLT was less than SSM+PLT (SSM < 29.89 kPa + PLT > 113.5 × 109/L) (35.7% vs. 44.1%), it was higher than that of the Baveno VI criteria (B6) (35.7% vs. 28.2%). We did not validate SSM+PLT in VC considering our aims. ST+PLT safely spared 24.6% of EGDs in VC, identical to B6. Conclusions: The ability of ST+PLT to exclude HRVs was superior to B6 but slightly inferior to SSM+PLT. When SSM cannot be routinely performed, ST+PLT provides an extra option for patients to exclude HRVs as a more convenient model.

Evaluation of the Clinical Characteristics of Dry Eye Secondary to Different Types of Liver Diseases.

INTRODUCTION: This study compares the clinical characteristics of dry eye secondary to primary biliary cholangitis (PBC), drug-induced liver injury (DILI), and viral hepatitis B(HBV) to evaluate the ocular surface damage caused by different types of liver diseases. METHODS: Thirty healthy people were included as control group. Sixty patients with dry eye secondary to different types of liver disease were included, including 19 cases of PBC, 18 cases of DILI, and 23 cases of HBV. All patients were evaluated by the SPEED questionnaire, corneal fluorescein staining (CFS), noninvasive tear breakup time (NIBUT), Schirmer I test (SIt), tear meniscus height test (TMH), the area of meibomian glands dropout (MG dropout), partial blinking rate (PBR), lipid layer thickness (LLT), meibum expressibility, and meibum quality. RESULTS: There are statistical differences in ophthalmic examination results between different types of liver diseases and normal people (P < 0.05). Compared with DILI and HBV groups, the CFS score of PBC group score was higher (P < 0.05), the PBR was higher (P < 0.05), and the SIt was lower (P < 0.01). The TMH of PBC and DILI groups were significantly lower than the HBV group, and the difference was statistically significant (P < 0.05). Compared with the PBC group, the LLT of the DILI group decreased (P < 0.01). The area of meibomian glands dropout of the three groups had mild-to-moderate defects, but there was no significant statistical difference between groups (P > 0.05).The Meibum quality score in the DILI group was significantly higher than the HBV group (P < 0.05). CONCLUSIONS: The PBC group was more prone to aqueous-deficient dry eye. The DILI group was more prone to obstructive meibomian gland dysfunction (MGD).The HBV group was more prone to nonobstructive MGD. The symptoms of dry eye in the PBC group are mild-to-moderate discomfort, but the degree of corneal damage is higher, indicating that the corneal sensitivity is reduced, which may be related to the high rate of partial blinking.

Senescence and senotherapies in biliary atresia and biliary cirrhosis.

BACKGROUND: Premature senescence occurs in adult hepatobiliary diseases and worsens the prognosis through deleterious liver remodeling and hepatic dysfunction. Senescence might also arises in biliary atresia (BA), the first cause of pediatric liver transplantation. Since alternatives to transplantation are needed, our aim was to investigate premature senescence in BA and to assess senotherapies in a preclinical model of biliary cirrhosis. METHODS: BA liver tissues were prospectively obtained at hepatoportoenterostomy (n=5) and liver transplantation (n=30) and compared to controls (n=10). Senescence was investigated through spatial whole transcriptome analysis, SA-ß-gal activity, p16 and p21 expression, γ-H2AX and senescence-associated secretory phenotype (SASP). Human allogenic liver-derived progenitor cells (HALPC) or dasatinib and quercetin (D+Q) were administrated to two-month-old Wistar rats after bile duct ligation (BDL). RESULTS: Advanced premature senescence was evidenced in BA livers from early stage and continued to progress until liver transplantation. Senescence and SASP were predominant in cholangiocytes, but also present in surrounding hepatocytes. HALPC but not D+Q reduced the early marker of senescence p21 in BDL rats and improved biliary injury (serum γGT and Sox9 expression) and hepatocytes mass loss (Hnf4a). CONCLUSIONS: BA livers displayed advanced cellular senescence at diagnosis that continued to progress until liver transplantation. HALPC reduced early senescence and improved liver disease in a preclinical model of BA, providing encouraging preliminary results regarding the use of senotherapies in pediatric biliary cirrhosis.

Autoantibodies testing in autoimmunity: Diagnostic, prognostic and classification value.

Diagnosis of autoimmune diseases is in most cases challenging for clinicians as there is not a single specific laboratory or histological marker to diagnose or exclude the presence of the conditions. This review focused on the current knowledge of the role of autoantibodies' testing in various diseases, such as systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, undifferentiated connective tissues disease, primary biliary cholangitis and primary sclerosing cholangitis. Similarly, the prognostic and diagnostic values of autoantibodies testing in patients with interstitial lung disease have been reviewed. In-depth research on the molecular action of these autoantibodies on immune regulation and diseases pathogenesis has been explored beyond their correlation with disease phenotypes, highlighting the impact of autoantibodies targeting on disease outcomes and etiopathogenesis.