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Orphanet Journal of Rare Diseases Aug 2022Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. The aim of the present study was to characterize the clinical features and...
BACKGROUND AND AIMS
Immunoglobulin G4-related disease (IgG4-RD) is a multisystem fibroinflammatory condition. The aim of the present study was to characterize the clinical features and therapeutic response of patients with IgG4-RD and identify risk factors for disease relapse.
METHODS
We collected baseline data of eligible patients with IgG4-RD and analyzed clinical features by interview and review of medical records. The patients who received glucocorticoids (GC) therapy with at least 3 months follow-up were used to characterize the therapeutic response and identify risk factors for relapse.
RESULT
Totally 127 IgG4-RD patients, including 92 males and 35 females, were enrolled in the present study. The median age of onset was 63.0 years, ranging from 23 to 86. The pancreas, bile duct and lymph nodes were the most frequently involved organs. The serum IgG4 level was elevated in 94.5% of the patients and was correlated with the number of organs involved. Patients classified as head and neck limited group were more likely to be female. Compared to Mikulicz syndrome and systemic involvement group, pancreato-hepatobiliary group had higher aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, bilirubin and lower IgG4 level. Mikulicz syndrome and systemic involvement group had the highest IgG4-RD RI score, IgG level. Among 92 patients who received medical therapy with at least 3 months follow-up, 76 received GC alone or in combination with immunomodulator (IM) and 16 patients did not take GC. 74 out of the 76 patients (97.3%) achieved remission, with 59 of them remained in remission and 15 of them relapsed. Whereas 16 patients did not take GC, among them, 6 patients achieved remission with one relapsed. On multivariate analysis, higher initial score of ACR/EULAR IgG4-RD Classification Criteria and GC withdrawal were independent predictors for relapse.
CONCLUSION
Four phenotypes of IgG4-RD showed different demographic and serological features. GC + IM therapy was safe and effective and might protect patients from relapse. The independent risk factors of relapse were GC withdrawal and higher score of ACR/EULAR IgG4-RD Classification Criteria.
Topics: China; Female; Glucocorticoids; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Immunologic Factors; Immunosuppressive Agents; Male; Recurrence; Retrospective Studies
PubMed: 35927746
DOI: 10.1186/s13023-022-02404-8 -
Pathology International May 2021In this review, the author shows that simultaneous multiple disorders caused by reactivation of Epstein-Barr virus can lead to salivary gland disorders as part of... (Review)
Review
In this review, the author shows that simultaneous multiple disorders caused by reactivation of Epstein-Barr virus can lead to salivary gland disorders as part of Sjogren's syndrome (SS). Therefore, clinicians must differentiate SS from other diseases when diagnosing and treating salivary gland disorders. In particular, the author explains how microbial infection in SS overcomes immunological tolerance, leading to pathological changes, and how cytokine overexpression and endocrine disrupters contribute to glandular tissue injury. Also, the author suggests that involvement of reactive oxygen species is a common pathogenesis of salivary gland disorders and SS, so regulation of oxidative stress is an effective treatment for both. The results of clinical studies on restoring salivary gland function and regenerating salivary glands with tissue stem cells may provide clues on elucidating the cause of SS.
Topics: Antioxidants; Arthritis, Rheumatoid; Autoantigens; Autoimmune Diseases; Cytokines; Diagnosis, Differential; Dioxins; Epstein-Barr Virus Infections; Estrogens; Female; Genetic Predisposition to Disease; Herpesvirus 4, Human; Humans; Interleukin-10; Lymphocytes; Male; Mikulicz' Disease; Oxidative Stress; Reactive Oxygen Species; Salivary Glands; Sjogren's Syndrome; Stem Cell Transplantation; Ubiquinone; Virus Activation; Virus Diseases
PubMed: 33751738
DOI: 10.1111/pin.13079 -
Reumatologia 2022IgG4-related disease is a potentially systemic disease mimicking and overlapping with different autoimmune diseases, such as primary Sjögren's syndrome (pSS). The...
OBJECTIVES
IgG4-related disease is a potentially systemic disease mimicking and overlapping with different autoimmune diseases, such as primary Sjögren's syndrome (pSS). The involvement of salivary glands, previously called Mikulicz's disease, has been reclassified as IgG4-related sialadenitis (SA). The aim of this study was to assess the prevalence of IgG4-SA in a cohort of Italian Caucasian patients presenting with xerostomia and to evaluate the eventual overlap between IgG4-SA and pSS.
MATERIAL AND METHODS
We included 154 patients - 15 males and 139 females, mean age 54.18 ±14.24 years, who underwent minor salivary gland biopsy between March and December 2019 for xerostomia. Histopathology was evaluated using Chisholm-Mason (CM) and focus score (FS) for pSS and immunohistochemical study with IgG4 staining for IgG4-SA were performed. Serum autoantibodies (anti-SSa/RoAb, anti-SSB/LaAb, antinuclear antibodies, rheumatoid factor) were also assessed.
RESULTS
In 69 patients (44.8%) FS 0 was found, while FS ≥ 1 was presented in 85 (55.2%). Chisholm-Mason score < 3 and CM ≥ 3 was found in 73 (47.4%) and 81 (52.6%) cases, respectively. IgG4/high-power field level was 20 in 3 pSS patients (1.9%), but none of them had an IgG4/IgG ratio ≥ 40, as well as tissue fibrosis with storiform pattern, obliterative vasculitis, and tissue eosinophilia. The diagnosis of pSS, was confirmed in 92 patients (59.74%). No patient was definitively diagnosed with an IgG4-related disease.
CONCLUSIONS
In the case of xerostomia, the evaluation of the histopathological specimen for IgG4 should not be routinely performed, at least in an Italian-based Caucasian population. Moreover, immunohistochemistry should not be requested in the case of a negative result of biopsy for pSS.
PubMed: 35645421
DOI: 10.5114/reum.2022.114207 -
Journal of the American College of... Jun 2024Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI). (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Empagliflozin reduces the risk of heart failure (HF) hospitalizations but not all-cause mortality when started within 14 days of acute myocardial infarction (AMI).
OBJECTIVES
This study sought to evaluate the association of left ventricular ejection fraction (LVEF), congestion, or both, with outcomes and the impact of empagliflozin in reducing HF risk post-AMI.
METHODS
In the EMPACT-MI (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction) trial, patients were randomized within 14 days of an AMI complicated by either newly reduced LVEF<45%, congestion, or both, to empagliflozin (10 mg daily) or placebo and were followed up for a median of 17.9 months.
RESULTS
Among 6,522 patients, the mean baseline LVEF was 41 ± 9%; 2,648 patients (40.6%) presented with LVEF <45% alone, 1,483 (22.7%) presented with congestion alone, and 2,181 (33.4%) presented with both. Among patients in the placebo arm of the trial, multivariable adjusted risk for each 10-point reduction in LVEF included all-cause death or HF hospitalization (HR: 1.49; 95% CI: 1.31-1.69; P < 0.0001), first HF hospitalization (HR: 1.64; 95% CI: 1.37-1.96; P < 0.0001), and total HF hospitalizations (rate ratio [RR]: 1.89; 95% CI: 1.51-2.36; P < 0.0001). The presence of congestion was also associated with a significantly higher risk for each of these outcomes (HR: 1.52, 1.94, and RR: 2.03, respectively). Empagliflozin reduced the risk for first (HR: 0.77; 95% CI: 0.60-0.98) and total (RR: 0.67; 95% CI: 0.50-0.89) HF hospitalizations, irrespective of LVEF or congestion, or both. The safety profile of empagliflozin was consistent across baseline LVEF and irrespective of congestion status.
CONCLUSIONS
In patients with AMI, the severity of left ventricular dysfunction and the presence of congestion was associated with worse outcomes. Empagliflozin reduced first and total HF hospitalizations across the range of LVEF with and without congestion. (Trial to Evaluate the Effect of Empagliflozin on Hospitalization for Heart Failure and Mortality in Patients with Acute Myocardial Infarction [EMPACT-MI]; NCT04509674).
Topics: Humans; Benzhydryl Compounds; Glucosides; Male; Female; Myocardial Infarction; Heart Failure; Middle Aged; Aged; Sodium-Glucose Transporter 2 Inhibitors; Ventricular Function, Left; Stroke Volume; Hospitalization; Double-Blind Method; Follow-Up Studies
PubMed: 38588929
DOI: 10.1016/j.jacc.2024.03.405 -
Advances in Clinical and Experimental... Oct 2022Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial...
BACKGROUND
Cardiovascular disease (CVD) is associated with intestinal barrier dysfunction and increased intestinal permeability. Increased intestinal permeability to gut microbial metabolites may accelerate the progression of CVD. Plasma citrulline levels are a marker of functional enterocyte mass, and reduced citrulline levels indicate intestinal epithelial damage. Citrulline was reported as a useful prognostic marker in critically ill patients. However, data are lacking on the association of citrulline with long-term mortality in patients with CVD and with the levels of trimethylamine N-oxide (TMAO), a microbiota-derived metabolite which has been implicated in the pathogenesis of CVD.
OBJECTIVES
To assess the effect of citrulline levels, a marker of intestinal barrier disruption, on long-term mortality in patients with CVD. Moreover, the relationship between the concentrations of 2 biomarkers - citrulline and TMAO - was assessed.
MATERIAL AND METHODS
Serum citrulline levels were retrospectively assessed in 1036 consecutive patients with CVD (median age: 62 years; 61% men) hospitalized between 2013 and 2015. Associations of citrulline levels with 5-year mortality rates as well as anthropometric and biochemical parameters were evaluated for the entire study group and in subgroups of patients with acute coronary syndrome (ACS), chronic coronary syndrome, chronic heart failure (chronic HF), and atrial fibrillation (AF). Correlations between serum citrulline and TMAO levels were assessed.
RESULTS
The median citrulline level in the study population was 22.5 μM (interquartile range (IQR): 17.8-27.9). Citrulline levels were not associated with 5-year mortality in patients with CVD (hazard ratio (HR) = 0.99; 95% confidence interval (95% CI): 0.97-1.00; p = 0.49). Median citrulline levels differed significantly between deceased patients and survivors at 5 years in patients with ACS (p = 0.025). There were no significant correlations between citrulline and TMAO levels (Kendall's tau = 0.027).
CONCLUSIONS
Decreasing citrulline levels do not predict long-term mortality of hospitalized patients with CVD. Moreover, they are not associated with the serum levels of TMAO in these patients.
Topics: Male; Humans; Middle Aged; Female; Citrulline; Cardiovascular Diseases; Retrospective Studies; Prognosis; Biomarkers; Acute Coronary Syndrome
PubMed: 35699588
DOI: 10.17219/acem/150475 -
Scientific Reports Jan 2021The clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Herein we evaluated their association with clinical...
The clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Herein we evaluated their association with clinical phenotypes, serology and activity in patients with IgG4-RD. Cross-sectional study that included 45 patients with IgG4-RD, and as controls 25 with Sjögren's syndrome (SS) and 15 with sarcoidosis. IgG4-RD patients were classified in clinical phenotypes: pancreato-hepato-biliary, retroperitoneum/aorta, head/neck-limited and Mikulicz/systemic; as well as proliferative vs. fibrotic phenotypes. We assessed the IgG4-RD Responder Index (IgG4-RD RI) at recruitment and measured IgG1, IgG4, κ and λ sFLC serum levels by turbidometry. sFLC levels were similar among IgG4-RD, SS and sarcoidosis groups. Regarding the IgG4-RD patients, the mean age was 49 years, 24 (53.3%) were men and 55.5% had activity. Eight (17.7%) belonged to pancreato-hepato-biliary, 6 (13.3%) to retroperitoneum/aorta, 14 (31.1%) to head/neck-limited, 16 (35.5%) to Mikulicz/systemic phenotypes, whereas 36 (80%) to proliferative and 9 (20%) to fibrotic phenotypes. High κ sFLC, λ sFLC and κ/λ ratio were present in 29 (64.4%), 13 (28.9%) and 13 (28.9%) of IgG4-RD patients, respectively. There were no differences in sFLC among IgG4-RD phenotypes. κ sFLC and κ/λ ratio correlated positively with the number of involved organs and IgG4-RD RI. Patients with renal involvement had higher κ sFLC and λ sFLC. The AUC for κ sFLC and λ sFLC, for renal involvement was 0.78 and 0.72, respectively. Active IgG4-RD had higher levels of κ sFLC and more frequently a high κ/λ ratio. The AUC for κ sFLC and κ/λ ratio for predicting active IgG4-RD was 0.67 and 0.70, respectively. sFLC correlated positively with IgG1 and IgG4 levels. sFLC may be useful as a biomarker of disease activity as well as multiorgan and renal involvement. In particular, a high κ/λ ratio may identify patients with active disease.
Topics: Adult; Biomarkers; Female; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Immunoglobulin Light Chains; Immunosuppressive Agents; Male; Middle Aged; Phenotype
PubMed: 33469111
DOI: 10.1038/s41598-021-81321-5 -
Journal of Clinical Rheumatology :... Sep 2022Data on IgG4-related disease (IgG4-RD) come almost exclusively from cohorts from Asia, Europe, and North America. We conducted this study to describe the clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/OBJECTIVE
Data on IgG4-related disease (IgG4-RD) come almost exclusively from cohorts from Asia, Europe, and North America. We conducted this study to describe the clinical presentation, phenotype distribution, and association with sex, ethnicity, and serological markers in a large cohort of Latin American patients with IgG4-RD.
METHODS
We performed a multicenter medical records review study including 184 Latin American IgG4-RD patients. We assigned patients to clinical phenotypes: group 1 (pancreato-hepato-biliary), group 2 (retroperitoneal/aortic), group 3 (head and neck-limited), group 4 (Mikulicz/systemic), and group 5 (undefined). We focused the analysis on how sex, ethnicity, and clinical phenotype may influence the clinical and serological presentation.
RESULTS
The mean age was 50.8 ± 15 years. Men and women were equally affected (52.2% vs 48.8%). Fifty-four patients (29.3%) were assigned to group 1, 21 (11.4%) to group 2, 57 (30.9%) to group 3, 32 (17.4%) to group 4, and 20 (10.8%) to group 5. Male sex was associated with biliary tract (odds ratio [OR], 3.4; 95% confidence interval [CI], 1.36-8.26), kidney (OR, 3.4; 95% CI, 1.28-9.25), and retroperitoneal involvement (OR, 5.3; 95% CI, 1.45-20). Amerindian patients presented more frequently with atopy history and gallbladder involvement. Group 3 had a female predominance.
CONCLUSIONS
Latin American patients with IgG4-RD were younger, and men and women were equally affected compared with White and Asian cohorts. They belonged more commonly to group 1 and group 3. Retroperitoneal and aortic involvement was infrequent. Clinical and serological features differed according to sex, ethnicity, and clinical phenotype.
Topics: Adult; Aged; Ethnicity; Female; Humans; Immunoglobulin G; Immunoglobulin G4-Related Disease; Latin America; Male; Middle Aged; Phenotype
PubMed: 35612589
DOI: 10.1097/RHU.0000000000001858 -
Viruses Sep 2022There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been...
There is accumulating evidence on the perinatal aspects of COVID-19, but available data are still insufficient. The reports on perinatal aspects of COVID-19 have been published on a small group of patients. Vertical transmission has been noted. The SARS-CoV-2 genome can be detected in umbilical cord blood and at-term placenta, and the infants demonstrate elevated SARS-CoV-2-specific IgG and IgM antibody levels. In this work, the analysis of clinical characteristics of RT-PCR SARS-CoV-2-positive pregnant women and their infants, along with the placental pathology correlation results, including villous trophoblast immunoexpression status for SARS-CoV-2 antibody, is presented. RT-PCR SARS-CoV-2 amniotic fluid testing was performed. Neonatal surveillance of infection status comprised RT-PCR testing of a nasopharyngeal swab and the measuring of levels of anti-SARS-CoV-2 in blood serum. In the initial study group were 161 pregnant women with positive test results. From that group, women who delivered during the hospital stay were selected for further analysis. Clinical data, laboratory results, placental histomorphology results, and neonatal outcomes were compared in women with immunohistochemistry (IHC)-con SARS-CoV-2-positive and IHC SARS-CoV-2-negative placentas (26 cases). A positive placental immunoprofile was noted in 8% of cases ( = 2), whereas 92% of cases were negative ( = 24). Women with placental infection proven by IHC had significantly different pathological findings from those without. One infected neonate was noted ( = 1; 4%). Infection was confirmed in perinatal autopsy, as there was the intrauterine fetal demise. The potential course of the infection with the risk of vertical transmission and implications for fetal-neonatal condition is critical for proper clinical management, which will involve comprehensive, multidisciplinary perinatal care for SARS-CoV-2-positive patients.
Topics: COVID-19; Female; Humans; Immunoglobulin G; Immunoglobulin M; Infant; Infant, Newborn; Infectious Disease Transmission, Vertical; Placenta; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2
PubMed: 36146849
DOI: 10.3390/v14092043 -
Rheumatology International Apr 2020Immunoglobulin IgG4 plays a role in the pathogenesis of the Mikulicz disease previously considered a form of primary Sjögren's syndrome (pSS). We investigated serum...
Immunoglobulin IgG4 plays a role in the pathogenesis of the Mikulicz disease previously considered a form of primary Sjögren's syndrome (pSS). We investigated serum levels of IgG4, total IgG, C3, and C4 serum complementary components in patients suspected of Sjögren's syndrome. Basic laboratory and immunological tests, including IgG4 and IgG concentration, were performed on 20 healthy and 68 suspected of pSS individuals. We distinguished: group I: 48 pSS patients; group II (sicca): 20 patients with dryness without pSS. We revealed: statistical differences between groups I and II concerning hypergammaglobulinemia, ESR, RF, ANA, Ro, and La antibodies; lower IgG4 levels and IgG4/IgG ratio in group I compared to healthy individuals (p < 0.0435; 0.0035, respectively); no significant differences in the concentrations of IgG4 and IgG4/IgG ratio between sicca and control groups. significantly lower (p < 0.0002) C4 levels in group I compared to other groups; significant differences in C4 concentration and IgG4/IgG ratio between three groups (p = 0.0002 and p = 0.0090, respectively); a weak negative correlation between C4 and IgG (r =- 0.274) in the whole database; weak positive correlation between C4 and IgG4/IgG ratio (r = 0.237); a negative correlation of IgG4, IgG4/Ig ratio and C4 with focus score (r = - 0.281; r = - 0.327; r = - 0.406, respectively). IgG4 serum levels were significantly decreased compared to healthy subjects. IgG4 and C4 levels correlated with infiltrations in minor salivary glands. Hypergammaglobulinemia and decreased serum C4 component levels are typical for pSS.
Topics: Adult; Case-Control Studies; Female; Humans; Hypergammaglobulinemia; Immunoglobulin G; Male; Middle Aged; Pilot Projects; Sjogren's Syndrome
PubMed: 32062697
DOI: 10.1007/s00296-020-04529-0 -
BMC Ophthalmology Jul 2023Sjögren's Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz's disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in...
BACKGROUND
Sjögren's Syndrome (SS) is an inflammatory autoimmune disease, and Mikulicz's disease (MD) is a lymphoproliferative disorder. Both MD and SS are more common in middle-aged female, and the dry eyes could be presented in both of them with different degree. The MD patients are characterized by symmetrical swelling of the lacrimal glands which also can occur in the early stage of SS. And the imaging findings between early stage of SS and MD are lack of specificity. Therefore, SS and MD have similarities in the clinical manifestations, imaging and pathological findings and are confused in diagnosis.
CASE PRESENTATION
A 51-year-old female patient presented with bilateral swelling of the upper eyelids for 2 years. She also reported having dry mouth and dry eyes which could be tolerated. The Schirmer's test result is positive and the laboratory tests indicate serum total IgG increased. In the bilateral lacrimal gland area could palpate soft masses. The orbital magnetic resonance imaging (MRI) examination showed bilateral lacrimal gland prolapse. While the histopathological result was considered as MD. The immunohistochemical (IHC) staining results were positive for IgG and negative for IgG4. To clarify the diagnosis, SS-related laboratory tests were performed: anti-SSA antibody (+++), anti-SSB antibody (+++), anti-Ro-52 antibody (+++). With a comprehensive consideration, the final diagnosis was SS.
CONCLUSION
When the clinical manifestations are atypical, it is necessary to pay attention to the differential diagnosis of SS and MD.
Topics: Middle Aged; Humans; Female; Mikulicz' Disease; Sjogren's Syndrome; Salivary Glands; Edema; Immunoglobulin G; Diagnostic Errors
PubMed: 37501055
DOI: 10.1186/s12886-023-03090-1