Clinical features of liver dysfunction in collagen diseases

Aim: Liver dysfunction is not rare in patients with collagen disease. We sought to elucidate the clinical features of liver dysfunction in the presence of collagen disease. Methods: We analyzed the frequency and causes of liver dysfunction in 607 patients (rheumatoid arthritis [RA], n = 220; systemic lupus erythematosus [SLE], n = 164; systemic sclerosis [SSc], n = 47; Sjögren's syndrome [SjS], n = 44; Behçet's disease, n = 43; polymyositis/dermatomyositis [PM/DM], n = 27; vasculitis syndrome, n = 25; mixed connective tissue disease [MCTD], n = 21; and adult‐onset Still's disease [AOSD], n = 16). Results: Liver dysfunction was observed in 238 (39.2%) of 607 patients showing collagen disease. Patients with AOSD (81.3%), PM/DM (51.9%) and vasculitis syndrome (48.0%) frequently displayed liver dysfunction. Liver dysfunction in collagen diseases results from many causes; drug‐induced liver injury (26.1%), fatty liver (7.6%), viral hepatitis (1.3%), autoimmune hepatitis (4.2%), primary biliary cirrhosis (15.9%) and the collagen disease itself (15.5%). Conversely, primary biliary cirrhosis was a leading cause in SSc (76.1%) and SjS (70.0%). Liver dysfunction in collagen disease tended to be mild. In addition, alanine aminotransferase levels correlated positively with ferritin levels in AOSD (R = 0.708, P < 0.05). Moreover, alkaline phosphatase levels correlated positively with C reactive protein levels in vasculitis syndrome (R = 0.833, P < 0.05). Conclusion: Liver dysfunction in the presence of collagen disease has various causes, and dysfunction associated with collagen disease reflects the activity of the collagen disease itself.     

Autoantibodies against C-reactive protein (CRP) in sera of patients with systemic rheumatic diseases

Abstract

An assessment of the frequency of serum autoantibodies against modified C-reactive protein (mCRP) in systemic rheumatic diseases and the association of these autoantibodies with clinical and laboratory findings in patients with systemic lupus erythematosus (SLE). Serum levels of autoantibodies against mCRP were measured by an enzyme-linked immunosorbent assay in 125 patients with SLE and in 213 patients with other systemic rheumatic diseases. The frequency of patients with high antimodified CRP antibody levels was 32% in SLE, 22% in systemic sclerosis (SSc), 19% in polymyositis/dermatomyositis (PM/DM), 43% in primary Sjögren's syndrome (pSS), 29% in rheumatoid arthritis (RA), 33% in mixed connective tissue disease (MCTD), and 43% in overlap syndrome. Serum levels of anti-mCRP antibody were significantly lower in SLE patients with persistent proteinuria (P < 0.001), cellular casts (P < 0.01), and hypoalbuminemia (P < 0.05). Serum anti-mCRP antibody levels in SLE showed a direct correlation with serum IgG levels (P < 0.001), serum anti-SS-A antibody levels (P < 0.01), serum anti-SS-B antibody levels (P < 0.01), and serum anti-U1-RNP antibody levels (P < 0.05). Inhibition experiments revealed that nonnative epitopes on the CRP molecule, termed mCRP, were the main target of the anti-mCRP antibodies detected. Autoantibodies against mCRP were frequently found in sera from patients with systemic rheumatic diseases, and may have a role in the immunopathogenesis of systemic rheumatic diseases, which are characterized by persistent inflammation.     

Anticyclic citrullinated peptide antibodies in patients with mixed connective tissue disease

Abstract

The clinical significance of anticyclic citrullinated peptide (CCP) antibodies in patients with mixed connective tissue disease (MCTD) was assessed. Altogether, 86 sera from MCTD patients, 96 from rheumatoid arthritis (RA) patients, 42 from systemic lupus erythematosus (SLE) patients, 23 from systemic sclerosis (SSc) patients, 21 from poymyositis/dermatomyositis (PM/DM) patients, and 17 from those with Sjögren’s syndrome (SjS) were tested for anti-CCP antibodies using an enzyme-lined immunosorbent assay. Among the 96 RA patients, anti-CCP antibodies were detected in 85%, with the frequency being significantly higher than in MCTD, SLE, SSc, PM/DM, and SjS patients (9%, 14%, 13%, 14%, and 18%, respectively; P < 0.001). Among eight MCTD patients who fulfilled the diagnostic criteria for RA, only 50% had anti-CCP antibodies, and the prevalence was significantly lower than for all RA patients (p < 0.01). All eight patients who fulfilled the criteria for RA had overlap of SLE and SSc, except one patient, whereas the four anti-CCP-positive patients who did not fulfill the criteria for RA had SjS without overlapping features of SLE and SSc; moreover, most of their antibody titers were low. These results suggested that anti-CCP antibodies are associated with RA in MCTD patients, but careful diagnosis of RA is required if patients with low titers of anti-CCP antibodies lack overlapping SLE and SSc.     

The diagnostic value of GerdQ in subjects with atypical symptoms of gastro-esophageal reflux disease

Background: Symptoms are essential in the clinical diagnosis of gastro-esophageal reflux disease (GERD). Questionnaires such as GerdQ have been developed as diagnostic aids. GerdQ has been thoroughly validated in well-characterized GERD patients, but has not yet been fully evaluated in a population that includes subjects with atypical symptoms.

Aim: To evaluate GerdQ in a population with typical and/or atypical symptoms of GERD, defined by 24-h pH monitoring. The secondary aim was to investigate the outcome of GerdQ depending on the response to proton pump inhibitor (PPI) treatment.

Methods: The study included 646 subjects referred for 24-h pH monitoring due to a clinical suspicion of GERD. All subjects completed GerdQ before performing a 24-h pH monitoring.

Results: In total, 377 (58%) subjects were diagnosed with GERD based on symptoms and 24-h pH monitoring (GERD_pH). Of these, 46% had atypical main symptoms. Overall, GerdQ (at cut-off 8) predicted GERD_pH with a sensitivity and specificity of 62% and 74%, respectively. A high specificity but poor sensitivity for diagnosis of GERD_pH was found for atypical main symptoms such as cough, dysphagia and globus. GerdQ had a relatively high sensitivity and specificity in predicting PPI response and a PPV of 99% at cut-off 8.

Conclusions: GerdQ has a diagnostic value in an unselected population presenting with typical and/or atypical symptoms of GERD, but a low sensitivity for diagnosis of GERD_pH was found in subjects with predominant symptoms such as cough, dysphagia and globus.     

Autoantibodies against C-reactive protein (CRP) in sera of patients with systemic rheumatic diseases

An assessment of the frequency of serum autoantibodies against modified C-reactive protein (mCRP) in systemic rheumatic diseases and the association of these autoantibodies with clinical and laboratory findings in patients with systemic lupus erythematosus (SLE). Serum levels of autoantibodies against mCRP were measured by an enzyme-linked immunosorbent assay in 125 patients with SLE and in 213 patients with other systemic rheumatic diseases. The frequency of patients with high antimodified CRP antibody levels was 32% in SLE, 22% in systemic sclerosis (SSc), 19% in polymyositis/dermatomyositis (PM/DM), 43% in primary Sjögren's syndrome (pSS), 29% in rheumatoid arthritis (RA), 33% in mixed connective tissue disease (MCTD), and 43% in overlap syndrome. Serum levels of anti-mCRP antibody were significantly lower in SLE patients with persistent proteinuria (P < 0.001), cellular casts (P < 0.01), and hypoalbuminemia (P < 0.05). Serum anti-mCRP antibody levels in SLE showed a direct correlation with serum IgG levels (P < 0.001), serum anti-SS-A antibody levels (P < 0.01), serum anti-SS-B antibody levels (P < 0.01), and serum anti-U1-RNP antibody levels (P < 0.05). Inhibition experiments revealed that nonnative epitopes on the CRP molecule, termed mCRP, were the main target of the anti-mCRP antibodies detected. Autoantibodies against mCRP were frequently found in sera from patients with systemic rheumatic diseases, and may have a role in the immunopathogenesis of systemic rheumatic diseases, which are characterized by persistent inflammation.     

Decreased CD161+CD8+ T cells in the peripheral blood of patients suffering from rheumatic diseases

OBJECTIVES: Although it has been reported that the numbers of both CD4(-)CD8(-) and CD4(+) natural killer T (NKT) cells are selectively decreased in the peripheral blood of patients with rheumatic diseases, there have been no reports concerning a novel subpopulation of CD8(+) NKT cells. To examine whether CD161(+)CD8(+) T cells, which are closely related to CD8(+) NKT cells, are also decreased in patients with rheumatic diseases, we have investigated the expression of CD161, together with that of CD28, CD25 and CD62L, on T cells in the peripheral blood of these patients. METHODS: The rheumatic diseases evaluated in this study were systemic lupus erythematosus (SLE) (n= 54), mixed connective-tissue disease (MCTD) (n= 15), systemic sclerosis (SSc) (n= 14), polymyositis/dermatomyositis (PM/DM) (n= 13) and rheumatoid arthritis (RA) (n= 24). Healthy donors were examined as controls (n= 18). The expression of CD161, CD28, CD25 and CD62L on T cells was analysed by flow cytometry. RESULTS: Both the frequency of CD161 expression on CD8(+) cells and the absolute number of CD161(+)CD8(+) cells were significantly decreased in patients with SLE, MCTD, SSc and PM/DM. Only the absolute number of CD161(+)CD8(+) T cells was significantly decreased in RA. CD161 expression on CD28(-)CD8(+) T cells was significantly decreased in SLE, MCTD and SSc. The absolute number of CD161(+)CD8(+)CD62L(-) T cells was significantly decreased in SLE, MCTD and SSc. CONCLUSIONS: Both the frequency and the absolute number of CD161(+)CD8(+) T cells were decreased in the peripheral blood of patients suffering from SLE, MCTD, SSc and PM/DM. This result suggests that there is also an abnormality of NKT cells in the CD8(+) population.     

HLA-DQB1 DPB1 alleles in Japanese patients with adult-onset Still’s disease

Abstract

Objective: HLA class II alleles are major determinants of genetic predisposition to rheumatic diseases. Predisposing effects of HLA had been suggested in AOSD, however, ethnic differences may account for variations in AOSD association with HLA. We determined the contribution of HLA-DQB1, DPB1 alleles to susceptibility to Adult-onset Still’s disease (AOSD) in the Japanese population.

Methods: HLA-DQB1 and DPB1 alleles were analyzed in 87 Japanese patients with AOSD and 413 Japanese healthy subjects.

Results: We found significant association between HLA-DQB1*06:02 (Pc?=?0.010, odds ratio: 2.54) and AOSD, whereas there was no association between the DQB1*06:02 allele and disease phenotypes of AOSD. Moreover, we did not find a predisposing effect of the HLA-DPB1 allele to AOSD. Haplotype analysis showed that presence of DRB1*15:01–DQB1*06:02 was associated with Japanese patients with AOSD. However, conditional logistic regression tests were unable to demonstrate independent association between DRB1*1501 or DQB1*0602 and AOSD.

Conclusions: Our results show significant association between AOSD and the HLA DQB1*06:02 allele, and between the DRB1*1501–DQB1*06:02 haplotype and AOSD susceptibility. These findings suggest that genetic susceptibility to AOSD depends on the genotype combinations of HLA DRB1 and DQB1 alleles.     

Upper esophageal sphincter abnormalities and high-resolution esophageal manometry findings in patients with laryngopharyngeal reflux

Background: The association between laryngopharyngeal reflux (LPR) and abnormalities of upper esophageal sphincter (UES) and esophageal motility is not clearly known. High-resolution esophageal manometry (HREM) has allowed accurate measurement and evaluation of UES and esophageal function.

Goals: To evaluate the UES function and esophageal motility using HREM in patients with LPR and compare them to patients with typical gastroesophageal reflux disease (GERD).

Study: All patients evaluated for GERD or LPR symptoms with esophageal function testing including HREM, ambulatory distal pH monitoring and upper endoscopy between 2006 and 2014 were retrospectively studied (n?=?220). The study group (group A, n?=?57) consisted of patients diagnosed with LPR after comprehensive evaluation. They were compared to patients who had typical GERD symptoms only (group B, n?=?98) and patients with both GERD and LPR symptoms (group C, n?=?65).

Results: Abnormalities in UES pressures and relaxation were found in about one-third of patients in all groups. There were no significant differences between the groups. Group B had higher prevalence of abnormal esophageal motility compared to others (group A vs. B vs. C?=?20.8% vs. 28% vs. 12.5%, p?=?.029). Group B patients also had higher prevalence of Barrett’s esophagus compared to others (group A vs. B vs. C?=?0% vs.12.2% vs. 4.6%, p?=?.01). Distal pH testing revealed no significant differences between the three groups.

Conclusions: Abnormal UES function was noted in one-third of patients with LPR or GERD. However, there were no abnormalities on esophageal function testing specific for LPR.     

Association of systemic and thyroid autoimmune diseases

Objective: There are few large cohort studies available on the association of systemic and thyroid autoimmune diseases. In this study, we wished to determine the association of Hashimotos thyroiditis (HT) and Graves disease (GD) with systemic autoimmune diseases. Methods: One thousand five hundred and seventeen patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), mixed connective tissue disease (MCTD), Sjögrens syndrome (SS) and polymyositis/dermatomyositis (PM/DM) were included in the study. The HT and GD were diagnosed based on thorough clinical evaluation, imaging and fine-needle aspiration cytology (FNAC). The frequency of HT and GD in these diseases was assessed. In addition, 426 patients with HT or GD were assessed and the incidence of SLE, RA, SSc, MCTD, SS and PM/DM among these patients was determined. Prevalence ratios indicating the prevalences of GD or HT among our autoimmune patients in comparison to prevalences of GD or HT in the general population were calculated. Results: Altogether 8.2% of systemic autoimmune patients had either HT or GD. MCTD and SS most frequently overlapped with autoimmune thyroid diseases (24 and 10%, respectively). HT was more common among MCTD, SS and RA patients (21, 7 and 6%, respectively) than GD (2.5, 3 and 1.6%, respectively). The prevalences of HT in SLE, RA, SSc, MCTD, SS and PM/DM were 90–, 160–, 220–, 556–, 176– and 69-fold higher than in the general population, respectively. The prevalences of GD in the same systemic diseases were 68-, 50-, 102-, 76-, 74- and 37-fold higher than in the general population, respectively. Among all thyroid patients, 30% had associated systemic disease. In particular, 51% of HT and only 16% of GD subjects had any of the systemic disorders. MCTD, SS, SLE, RA, SSc and PM/DM were all more common among HT patients (20, 17, 7, 4, 2 and 2%, respectively) than in GD individuals (2, 5, 5, 1, 2 and 1%, respectively). Conclusion: Systemic and thyroid autoimmune diseases often overlap with each other. HT and GD may be most common among MCTD, SSc and SS patients. On the other hand, these systemic diseases are often present in HT subjects. Therefore it is clinically important to screen patients with systemic autoimmune diseases for the co-existence of thyroid disorders.Take home message: Autoimmune thyroid diseases, such as Hashimotos thyroiditis and Graves disease are often associated with systemic autoimmune diseases, most commonly with Sjögrens syndrome and mixed connective tissue disease.     

Anticyclic citrullinated peptide antibodies in patients with mixed connective tissue disease

The clinical significance of anticyclic citrullinated peptide (CCP) antibodies in patients with mixed connective tissue disease (MCTD) was assessed. Altogether, 86 sera from MCTD patients, 96 from rheumatoid arthritis (RA) patients, 42 from systemic lupus erythematosus (SLE) patients, 23 from systemic sclerosis (SSc) patients, 21 from poymyositis/dermatomyositis (PM/DM) patients, and 17 from those with Sjögrens syndrome (SjS) were tested for anti-CCP antibodies using an enzyme-lined immunosorbent assay. Among the 96 RA patients, anti-CCP antibodies were detected in 85%, with the frequency being significantly higher than in MCTD, SLE, SSc, PM/DM, and SjS patients (9%, 14%, 13%, 14%, and 18%, respectively; P < 0.001). Among eight MCTD patients who fulfilled the diagnostic criteria for RA, only 50% had anti-CCP antibodies, and the prevalence was significantly lower than for all RA patients (p < 0.01). All eight patients who fulfilled the criteria for RA had overlap of SLE and SSc, except one patient, whereas the four anti-CCP-positive patients who did not fulfill the criteria for RA had SjS without overlapping features of SLE and SSc; moreover, most of their antibody titers were low. These results suggested that anti-CCP antibodies are associated with RA in MCTD patients, but careful diagnosis of RA is required if patients with low titers of anti-CCP antibodies lack overlapping SLE and SSc.     

Identification of autoantibodies to the I protein of the heterogeneous nuclear ribonucleoprotein complex in patients with systemic sclerosis

Objective. To assess the presence of autoantibodies to the I protein (polypyrimidine-tract binding protein) of the heterogeneous nuclear RNPs (hnRNP) in different connective tissue diseases. Antibodies to other hnRNP proteins (A1, A2, and B) have been previously found in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD). Methods. Sera from 101 patients with various connective tissue diseases and 25 normal controls were investigated by enzyme-linked immunosorbent assay and immunoblotting, for their reactivity to highly purified recombinant hnRNP I. Moreover, reactivity to cellular hnRNP I protein was investigated by immunoblotting using a partially purified preparation of hnRNP proteins (including A1, A2, B, and I), and by indirect immunofluorescence. For the analysis of the fluorescence pattern, affinity-purified antibodies to hnRNP I, obtained from a selected patient, were tested on HEp-2 cells. Results. By immunoblotting, antibodies reacting to recombinant hnRNP I were found in 22 of 40 patients with systemic sclerosis (SSc), 3 of 32 with RA, 0 of 23 with SLE, and 0 of 6 with MCTD. Antibodies to recombinant hnRNP I were more frequently found in patients with pre-SSc or limited SSc (15 of 24) than in those with intermediate or diffuse SSc (7 of 16). In indirect immunofluorescence studies, affinity-purified anti—hnRNP I autoantibodies gave a diffuse nucleoplasmic staining. Using an hnRNP preparation from nuclear extracts, anti—hnRNP I reactivity was detectable in SSc sera, while it was not detectable in RA, SLE, and MCTD sera reacting with hnRNP A/B proteins. Conclusion. Human autoimmune sera show distinct patterns of anti-hnRNP reactivity, i.e., anti-A/B in SLE and RA sera, and anti-I in SSc sera. This suggests that A/B proteins and the I protein may be involved in different dynamic hnRNP complexes that elicit different autoimmune responses. From a clinical perspective, anti—hnRNP I antibodies are frequently associated with pre-SSc features, suggesting an early appearance of these antibodies during the course of the disease.     

Visfatin levels and intima-media thicknesses in rheumatic diseases

Chronic inflammatory rheumatic diseases lead to increased prevalence of atherosclerosis. However, this early and accelerated atherosclerosis cannot be explained by traditional cardiovascular risk factors alone. The permanent overexpression of cellular adhesion molecules and pro-inflammatory cytokines in chronic inflammatory conditions may participate in accelerated atherosclerosis. Visfatin, a novel adipocytokine, has a potential insulin-like action and pro-inflammatory effects. Therefore, the aim of the study was to determine serum visfatin level and its association with common carotid intima-media thickness (IMT), which is a predictor of atherosclerosis, in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Behçet’s disease (BD). The study involved 29 RA, 26 SLE, 25 SSc, 30 BD patients, and 29 healthy controls (HC). Serum levels of TNF-α, IL-6, and visfatin were analyzed using enzyme-linked immunosorbent assay method and homeostasis model assessment for insulin resistance (HOMA-IR) indexes, and IMTs were determined. Serum visfatin level was higher in the RA group than all the other groups. In addition, visfatin level was higher in the active BD subgroup than the inactive BD subgroup. In the study groups, visfatin levels were not correlated with HOMA-IR indexes and IMTs. Whereas visfatin serum concentration was not associated with insulin resistance and carotid atherosclerosis in selected rheumatic diseases, it was higher in the RA and active BD groups, but not in the SLE and SSc groups. Visfatin levels may be associated with Th1/Th2 balance. Further studies are needed for more precise elucidation of the pro-inflammatory activities of visfatin.     

Frequency,characteristics and outcome of corona virus disease 2019 (COVID-19) infection in Iranian patients with rheumatic diseases

Aim of the workTo investigate the frequency, clinical characteristics and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in rheumatic diseases patients.Patients and methodsOne thousand patients with rheumatic diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), psoriatic arthritis (PsA), axial spondyloarthritis (SpA), systemic sclerosis (SSc), Sjögren’s syndrome (SS), Behçets disease (BD), vasculitis, idiopathic inflammatory myositis (IIM), relapsing polychondritis, sarcoidosis and antiphospholipid syndrome (APS) were studied. The following data were collected: age, sex, disease diagnosis, rheumatic disease medication. Rheumatic diseases patients were divided into two groups of infected and non-infected patients with COVID-19 and collected data were compared.ResultsThe 1000 patients mean age was 43.4 ± 13 years and 84.1% were females. The main diagnosis was RA (37.1%), followed by SLE (23.8%), SpA (13.4%), SSc (12.4%), vasculitis, BD and rhupus in 2.4%, 2.3% and 2.2% respectively, SS and SSc in 0.7% each. Most patients were taking glucocorticoids (78.4%). A large majority of patients were taking at least one of the cDMARDs. 16.1% were taking biologic therapy. 221 rheumatic diseases patients with COVID-19 were identified. Of these, 38 patients (17.2%) were hospitalized and 9 patients (4.1%) died. No significant difference was observed for compared variables in patients with and without COVID-19 except for prednisolone >20 mg/d (0.64% vs 2.26%; p = 0.048).ConclusionMost rheumatic diseases do not seem to be a risk factor for developing COVID-19 infection and despite immunosuppressive therapies, there is no poorer outcome. Only, patients using prednisolone >20 mg/d are at higher risk of developing COVID-19 infection.     

Pregnancy and rheumatic disorders

Autoimmune rheumatic diseases commonly affect young women with child-bearing potential. It is important to know the impact of these diseases on pregnancy, and conversely the effect of pregnancy on these diseases, which may have important implications for mothers and neonates. Majority of studies suggest that pregnancy aggravates systemic lupus erythematosus (SLE) disease activity while ameliorating the symptoms of rheumatoid arthritis (RA). This contrasting finding between RA and SLE in pregnancy is postulated to be due to the differences in autoimmune response. There is a raised Th2 type response during pregnancy in comparison to the non-pregnant state, leading to the over expression of Th2 cytokines, such as IL-4 and IL-10. These cytokines are believed to increase the autoantibody response in SLE but to be immunosuppressive in RA. Studies suggest that patients of systemic sclerosis and mixed connective tissue disorder (MCTD) also have worsening of their underlying disorder while paucity of data precludes any solid conclusion regarding disease activity in patients of Sjogren's syndrome. Pregnancies in SLE, RA, systemic sclerosis (SSc) and MCTD patients are associated with a greater risk of relatively poor foetal outcome than in the general population, especially with increased disease activity before conception and early in pregnancy. This review provides an update regarding the effect of pregnancy on autoimmune rheumatic disorders and vice-versa.     

Bronchoalveolar lavage fluid cells in mixed connective tissue disease

OBJECTIVE: Patients with mixed connective tissue disease (MCTD) exhibit clinical features of systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and polymyositis and dermatomyositis (PM-DM). The objective of this study was to clarify differences in BAL findings and immunophenotypes of BAL fluid (BALF) cells of patients with interstitial lung disease associated with these diseases. METHODOLOGY: We were unable to recruit a sufficient number of SLE patients with lung disease. We compared immunophenotypes of lymphocytes and alveolar macrophages (AM) in BALF of 20 MCTD patients with those of 21 SSc and 27 PM-DM patients and tested the relationships between immunophenotypes and pulmonary function in MCTD. RESULTS: MCTD patients had a significantly higher CD4/CD8 ratio with more CD4 positive lymphocytes than PM-DM patients (P = 0.025). In AM phenotypes, MCTD patients had a significantly lower percentage of CD71 positive AM compared with SSc patients (P = 0.023). DLCO was negatively related to absolute numbers of CD8 positive lymphocytes (R = -0.517, P= 0.033). CONCLUSIONS: CD4 positive lymphocytes in BALF were increased in MCTD compared to PM-DM patients, while CD71 positive AM were decreased in MCTD compared to SSc patients. CD8 positive lymphocytes correlated negatively with DLCO measurements in MCTD patients.     

Long-term outcomes of patients with symptomatic gastroesophageal reflux disease treated with vonoprazan

Objective: The novel potassium-competitive acid blocker, vonoprazan, provides rapid and effective acid suppression. The aim of this study is to evaluate the long-term outcomes of patients with symptomatic gastroesophageal reflux disease (GERD) treated with vonoprazan.

Methods: This retrospective cohort study included 55 patients with symptomatic GERD treated with vonoprazan who have been followed for more than one year. The effectiveness of vonoprazan on gastrointestinal symptoms was evaluated using the Izumo scale, a self-reported questionnaire reflecting quality of life related to various abdominal symptoms.

Results: These 55 patients with symptomatic GERD had non-erosive reflux disease (n?=?30) or erosive esophagitis (n?=?25). Vonoprazan (10?mg) for one month improved GERD symptoms in 89% (responders) and the improvement was maintained at one year in 82% without additional treatment. One-year maintenance therapy resulted in sustained resolution of GERD symptoms in 47%. Of the 49 responders, nine patients had relapse of GERD symptoms and dose escalation of vonoprazan improved the symptoms in six patients. Postprandial distress and the presence of erosive esophagitis before starting vonoprazan were identified as significant negative and positive predictors of sustained resolution of GERD symptoms for one year, respectively. Epigastric pain, postprandial distress, constipation and diarrhea were significantly improved at one-month and maintained at one year. After one-year of treatment, the endoscopic healing rate of erosive esophagitis was 95%.

Conclusion: One-year treatment with vonoprazan significantly improves GERD symptoms and endoscopic healing of erosive esophagitis is satisfactory. The long-term use of vonoprazan is effective and useful to control GERD.     

Autoimmune response to the spliceosome

Objective. To assess the significance of autoantibodies to RA33, the A2 protein of the heterogeneous nuclear ribonucleoproteins (hnRNP), and to the related hnRNP proteins A1, B1, and B2 in rheumatic diseases. Methods. Using a partially purified preparation of hnRNP-A and hnRNP-B proteins, sera from 303 patients with various rheumatic diseases were investigated by immunoblotting. For the analysis of crossreactivities, autoantibodies were affinity purified by blot elution. Results. Anti-A2/RA33 was found in 35% of rheumatoid arthritis (RA) patients, 38% of mixed connective tissue disease (MCTD) patients, 23% of systemic lupus erythematosus (SLE) patients, and, apart from single exceptions, not in patients with other rheumatic diseases. All anti-A2/RA33-positive sera were also reactive with B1 and B2, and anti-A2/RA33 antibodies cross-reacted with both proteins. Antibodies to hnRNP-A1 were found less frequently; moreover, the majority of anti-A1-positive sera also contained anti-A2/RA33 antibodies. In anti-A1, anti-A2/RA33 doublepositive sera, cross-reactivity between the 2 antibodies was generally observed. In SLE patients, the presence of anti-A2/RA33 was correlated with the presence of anti-(U1) small nuclear RNP (snRNP) and anti-Sm (P < 0.0001 and P < 0.005, respectively), but there was no evidence for cross-reactivity between antibodies to hnRNP and antibodies to snRNP antigens. Conclusion. Since both hnRNPs and snRNPs are essential components of the spliceosome, the data show that the immune systems of patients with RA, SLE, and MCTD react to this functional complex. However, compared with MCTD and SLE patients, RA patients have a more restricted immune response to the spliceosome: they react to hnRNP proteins, particularly to hnRNP-A2/RA33, but not to snRNPs.     

Residual symptoms and disease burden among patients with rheumatoid arthritis in remission or low disease activity: a systematic literature review

Objectives: To identify, describe and summarize evidence on residual symptoms and disease burdens in rheumatoid arthritis (RA) patients qualified as being in remission or low disease activity (LDA).

Methods: A systematic literature review (SLR) was conducted according to Cochrane collaboration guidelines. The population of interest was adult patients with RA in remission or LDA. The reported outcomes of interest were any symptoms or burdens.

Results: Fifty-one publications were identified through an eDatabase search. Together with 17 articles found through other sources, 68 were included for full text review. The most commonly reported residual symptoms were pain (number of studies?=?25), fatigue (n?=?21) and morning stiffness (n?=?5). Reported disease burdens included mental health (n?=?15), sleep disturbances (n?=?7) and work productivity (n?=?5), impairment in quality of life (n?=?21), and functional disability (n?=?34). Substantial residual symptoms and disease burdens were found to be present in patients in remission or LDA.

Conclusion: This is the first SLR to investigate residual symptoms and disease burdens in RA patients in remission or LDA. The results indicate that despite achieving conventional clinical targets, the disease continues to affect patients, suggesting the existence of unmet need under the current treatment paradigm.