•DM and PEI affect one third and half of patients with AIP at diagnosis respectively.•DM and PEI are more frequent in type 1 AIP compared to type 2 AIP.•Treatment with GCs increases the risk of ...developing DM in AIP patients.
Autoimmune pancreatitis (AIP) is a rare form of pancreatitis that may lead to endocrine and exocrine insufficiency if left untreated. AIP clinically responds to glucocorticoids (GCs) therapy, but multiple GCs courses are often required to maintain remission with detrimental effects on glycaemic control.
In this systematic review and meta-analysis, we aimed to assess the rate of endocrine and of exocrine insufficiency at diagnosis and at follow up in patients with AIP as well as the impact of GC therapy on pancreatic function in the long-term.
The MEDLINE, SCOPUS, and EMBASE databases were searched from inception to August 2021 to identify studies reporting data on endocrine and exocrine insufficiency in patients with AIP. Pooled events were calculated using a random-effect model and expressed in terms of pooled prevalence rates.
A total of 6522 AIP patients and sixty-two studies were included in the analysis. The pooled estimate rate for the overall prevalence of diabetes in AIP at baseline was 37% (95% CI 32-42, I2 96%). The pooled prevalence rate of exocrine insufficiency was 45% (95%CI 32.9-57.4; I2 97%). The pooled estimate rate of diabetes at follow-up was 44% (95%CI 26.1-62.4) in studies where GCs were given to 100% of patients and 42% (95%CI 30.6-52.9) in studies where GCs were given to less than 100% of patients.
A large proportion of patients with AIP displays concomitant exocrine and endocrine insufficiency at the time of diagnosis. The incidence of diabetes at the longest available follow up tends to increase in patients treated with GCs.
•Univocal strategies to maintain IgG4-RD remission are lacking.•Rituximab every 6 months prevents IgG4-RD flare with no major adverse events.•Rituximab 1 g every 6 months should be considered as ...remission maintenance strategy.
IgG4-Related Disease (IgG4-RD) promptly responds to glucocorticoids but relapses in most patients. Rituximab (RTX) represents a promising strategy to avoid IgG4-RD flares but its administration for maintaining disease remission has never been assessed in terms of optimal timing of infusion, dosage, and duration of treatment. In the present study we aimed to evaluate the efficacy and safety of RTX for maintenance of IgG4-RD remission.
Fourteen patients with IgG4-RD were treated with RTX as induction of remission therapy at the San Raffaele Scientific Institute in Milan, Italy. The cohort was then divided into two study groups: patients re-treated only in case of disease relapse (Group 1, n = 7), and patients regularly re-treated with RTX every 6 months for maintenance therapy (Group 2, n = 7). Data on free-relapse rate and adverse events were collected and retrospectively analysed.
Median follow-up time and baseline clinical-serological features were similar between Group 1 and 2 (p > 0.05). The free relapse rate 18 months after induction of remission treatment was significantly lower in Group 1 (29%) than in Group 2 (100%) (p = 0.006). Infectious complications developed in 6/14 patients (3 in Group 1 and 3 in Group 2).
Administration of RTX every 6 months as maintenance of remission therapy prevents IgG4-RD flares.
Objective
An unconventional population of CD4+ signaling lymphocytic activation molecule family member 7–positive (SLAMF7+) cytotoxic effector memory T (TEM) cells (CD4+ cytotoxic T lymphocytes CTLs) ...has been linked causally to IgG4‐related disease (IgG4‐RD). Glucocorticoids represent the first‐line therapeutic approach in patients with IgG4‐RD, but their mechanism of action in this specific condition remains unknown. We undertook this study to determine the impact of glucocorticoids on CD4+ CTLs in IgG4‐RD.
Methods
Expression of CD8α, granzyme A, perforin, and SLAMF7 within the effector memory compartment of CD45RO+ (TEM) and CD45RA+ effector memory T (TEMRA) CD4+ cells was quantified by flow cytometry in 18 patients with active IgG4‐RD, both at baseline and after 6 months of glucocorticoid treatment. Eighteen healthy subjects were studied as controls. Next‐generation sequencing of the T cell receptor α‐ and β‐chain gene was performed on circulating CD4+ CTLs from patients with IgG4‐RD before and after treatment and in affected tissues.
Results
Circulating CD4+ TEM and TEMRA cells were not expanded in IgG4‐RD patients compared to healthy controls. CD4+SLAMF7+ TEM cells (but not TEMRA cells) were significantly increased among IgG4‐RD patients. Within CD4+SLAMF7+ TEM cells, CD8α− cells but not CD8αlow cells were elevated in IgG4‐RD patients. The same dominant clones of CD8α−CD4+SLAMF7+ TEM cells found in peripheral blood were also identified in affected tissue. CD8α− and CD8αlowCD4+SLAMF7+ TEM cells both expressed cytolytic molecules. Clonally expanded CD8α− but not CD8αlowCD4+SLAMF7+ TEM cells decreased following glucocorticoid‐induced disease remission.
Conclusion
A subset of CD8α−CD4+SLAMF7+ cytotoxic TEM cells is oligoclonally expanded in patients with active IgG4‐RD. This TEM cell population contracts following glucocorticoid‐induced remission. Further characterization of this cell population may provide prognostic information and targets for therapeutic intervention.
•The 2019 ACR/EULAR Classification criteria for IgG4-RD represent a replicable instrument for classifying patients.•The 2019 ACR/EULAR Classification criteria for IgG4-RD provide a useful framework ...for orienting diagnosis.•The 2019 ACR/EULAR Classification criteria for IgG4-RD do not predict disease outcomes.
The 2019 ACR/EULAR Classification Criteria for IgG4-related disease (IgG4-RD) represent a fundamental tool for patient enrollment in research studies and in clinical trials but their usefulness in daily clinical practice remains unknown.
To validate the 2019 ACR/EULAR Classification Criteria for IgG4-RD in a real-life setting and to anticipate their utility for orienting disease diagnosis and patient management.
Four experts were asked to classify 200 patients diagnosed with IgG4-RD according to the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Agreement between experts was calculated and the Classification score of each patient was correlated with the following variables and outcomes: serum IgG4 and IgE; inflammatory markers; eosinophils; plasmablasts; IgG4-RD responder index; diabetes, osteoporosis, relapses; and use of rituximab.
Among the 157/200 cases equally rated by at least three experts, 94 (59.9%) achieved IgG4-RD classification and 63 (40.1%) did not. Strong agreement among IgG4-RD experts was observed in classifying patients (k = 0.711, p<0.0001). Clinical presentations not included in the classification algorithm and lack of informative histology were the most common reasons for not achieving classification. In patients achieving classification, the Classification score did not correlate with variables of disease activity and was not associated with specific outcomes.
The ACR/EULAR Classification Criteria represent a replicable instrument for classifying patients and a useful framework for orienting diagnosis but are of limited utility for assessing IgG4-RD activity, for predicting disease outcomes, and for defining personalized therapeutic approaches.
Autoimmune Pancreatitis (AIP) is a rare chronic inflammatory disease affecting the pancreas. Chronic pancreatic inflammation represents a risk factor for pre-neoplastic conditions such as Intraductal ...Papillary Mucinous Neoplasia (IPMN). Due to the rarity of AIP, the incidence, and clinical features of IPMN occurring in AIP patients remains unknown.
In the present study we aimed to explore the relationship between AIP and IPMN and to characterize the clinical features and outcomes of IPMN occurring in the context of AIP.
We retrospectively (2008–2020) analyzed the clinical and radiological records of a large single center cohort of patients with AIP and investigated the prevalence of IPMN. We then compared the clinical, laboratory and radiological characteristics of patients with IPMN and AIP with a cohort of patients with isolated IPMN.
Five hundred and nineteen patients were included in this retrospective study. Sixteen patients had concomitant IPMN and AIP(3%); 61 patients had isolated AIP (12%); 442 patients had isolated IPMN (85%). The prevalence of IPMN in patients with AIP was higher than that observed in the general population (21%vs8-10%). Worrisome Features and High-Risk Stigmata were more frequently observed in IPMN occurring together with AIP compared to isolated IPMN(p < 0.05). Based on radiological features IPMN in the context of AIP was more frequently of main-duct type compared to isolated IPMN(p < 0.05).
Our data suggest that AIP represents a chronic inflammatory condition that might favor IPMN development with high-risk features. Prolonged surveillance of these patients and longitudinal studies are required to further test the association with AIP and malignant and pre-malignant conditions.
Emerging therapy options for IgG4-related disease Lanzillotta, Marco; Fernàndez-Codina, Andreu; Culver, Emma ...
Expert review of clinical immunology,
05/2021, Letnik:
17, Številka:
5
Journal Article
Recenzirano
Awareness of IgG4-related disease (IgG4-RD) is increasing worldwide and specialists are now familiar with most of its clinical manifestations and mimickers. IgG4-RD promptly responds to ...glucocorticoids and repeated courses are typically used to induce and maintain remission because the disease relapses in most patients. If left untreated, it can lead to organ dysfunction, organ failure and death. Advancement in our understanding of IgG4-RD pathogenesis is leading to the identification of novel therapeutic targets and emerging treatments are now setting the stage for personalized therapies for the future.
This review focuses on emerging treatment options for IgG4-RD based on our advancing understanding of disease pathophysiology. Research was performed in the English literature on Pubmed and clinicaltrials.gov databases.
Glucocorticoids remain the first-line induction treatment for the multi-organ manifestations of IgG4-RD. Alternative immunosuppressive agents for maintaining remission are warranted in order to avoid long-term steroid toxicity, and to offer a more mechanistic and personalized therapeutic strategy. Targeting B and T-lymphocyte activation represents the most promising approach, but randomized controlled trials are eagerly awaited to confirm positive preliminary experiences reported in case series and small cohort studies.
PDF
