Immunopathogenesis of granulomas in chronic autoinflammatory diseases

Timmermans, Wilhelmina Maria Cornelia; Laar, Jan A. M. van; Hagen, P M van; Zelm, Menno C. van

doi:10.1038/cti.2016.75

Cited by 70 publications

(54 citation statements)

References 194 publications

(308 reference statements)

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“…Burillo‐Martinez et al described a woman receiving single agent pembrolizumab (2 mg/kg every 3 weeks) for melanoma metastatic to the peritoneum who developed a granulomatous mostly lobular panniculitis with some involvement of the septum, but without evidence of necrosis or vasculitis—features remarkably similar to our cases . The formation and maintenance of sarcoidal granulomas involves an array of cytokines and chemokines promoting CD4+ T helper 1 cell (Th1) response . Thus, the extent of cytokine imbalance and Th1 response may impact granuloma formation in a subset of patients on immune checkpoint therapy.…”

Section: Discussionmentioning

confidence: 99%

“…37 The formation and maintenance of sarcoidal granulomas involves an array of cytokines and chemokines promoting CD4+ T helper 1 cell (Th1) response. 49 Numerous reports have previously described the emergence of panniculitis in the context of systemic-targeted therapies against oncogenic kinase mutations. The vast majority of these occur in patients treated with BRAF inhibitor therapy (dabrafenib or vemurafenib), with occasional cases also occurring in patients receiving dabrafenib in combination with the MEK inhibitor trametinib.…”

Section: Casementioning

confidence: 99%

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Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients

et al. 2017

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Immunotherapies targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1) receptor and its ligand (PD-L1) have showed substantial therapeutic benefit in patients with clinically advanced solid malignancies. However, autoimmune toxicities are common and often significant adverse events with these agents. While rash and pruritus remain the most common cutaneous complications in treated patients, novel dermatologic toxicities related to immune checkpoint blockade continue to emerge as the number of patients exposed to immunotherapy increases. Here, we describe 2 patients treated with combination immunotherapy with ipilimumab and nivolumab who developed painful subcutaneous nodules. Although the findings were clinically concerning for disease recurrence, histopathologic examination of biopsies from the lesions revealed a subcutaneous mixed septal and lobular erythema nodosum-like panniculitis. Notably, neither patient received immunosuppressive therapy for these lesions, which subsequently remained stable, and both patients' cancer remained controlled. These cases show that the dermatologic toxicity profile of immune checkpoint blockade is diverse and continues to expand, and illustrates that recognition of such toxicities is critical to optimal patient management.

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Section: Discussionmentioning

confidence: 99%

Section: Casementioning

confidence: 99%

Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients

et al. 2017

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“…Non-caseating Granulomatous inflammation is considered a type IV immune reaction [6] . It forms as the activated T lymphocytes, induced by a foreign antigen, secrete a specific set of interleukins and chemo attractants [6] .…”

Section: Discussionmentioning

confidence: 99%

Pembrolizumab reactivates pulmonary granulomatosis

Al-dliw

Megri

Shahoub

et al. 2017

Respiratory Medicine Case Reports

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Sarcoid like reaction is a well-known entity that occurs as a consequence to several malignancies or their therapies. Immunotherapy has gained a lot of interest in the past few years and has recently gained approval as first line therapy in multiple advanced stage malignancies. Pneumonitis has been described as complication of such therapy. Granulomatous inflammation has been only rarely reported subsequent to immunotherapy. We describe a case of granulomatous inflammation reactivation affecting the lungs in a patient previously exposed to Pembrolizumab and have evidence of a distant granulomatous infection. We discuss potential mechanisms of the inflammation and assert the importance of immunosuppression in controlling the dis-inhibited immune system.

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“…For example, patients with CD also display reductions in the number of blood IgM memory B-cells, although they have normal numbers of Ig class-switched memory cell plasma cells [25, 26], and transitional B cells were expanded, which could be results of impaired generation from the splenic marginal zone [27]. According to Timmermans et al [28], the immunosuppressive drugs used to treat CD, especially TNF-α blockers, affect the B-cell compartment. Subsequently, disease exacerbation in treated patients could reflect a protective role of B cells in CD [29].…”

Section: Discussionmentioning

confidence: 99%

B1a Lymphocytes (CD19+CD5+) Deficiency in Patients with Crohn’s Disease and Its Relation with Disease Severity

Gil-Borrás

García‐Ballesteros

Benet-Campos

et al. 2018

Dig Dis

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Background/Aims: B1a cells (CD19+CD5+) are considered elements of the innate immune system. The aim of this study was to evaluate the frequency of B1a cells in the peripheral blood of patients with Crohn’s disease (CD) and its relation with disease severity. Methods: In this prospective study, a total of 128 subjects (64 CD patients and 64 healthy controls) were studied. B1a cells in peripheral blood, CD Activity Index, and Simple Endoscopic Score of B1a cells were studied. Results: A significant decrease of B1a cells in peripheral blood was observed in patients with CD versus controls (p = 0.002), especially in perforating or penetrating patterns (p = 0.017). A lower frequency of B1a cells is related to increased endoscopic severity (Spearman’s Rho: –0.559, p = 0.004). The mean frequency of B1a cells in patients with pre- and post-study surgery was significantly lower than that in patients who did not undergo surgery (p = 0.050 and p = 0.026, respectively). Conclusions: The B1a cell count in peripheral blood is lower in CD patients. This decrease is directly related to the severity of the disease (penetrating or perforating, Simple Endoscopy Score and surgery complication). These results pointed to the fact that B1a cells play an important role in immune protection in CD.

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Immunopathogenesis of granulomas in chronic autoinflammatory diseases

Cited by 70 publications

References 194 publications

Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients

Erythema nodosum‐like panniculitis mimicking disease recurrence: A novel toxicity from immune checkpoint blockade therapy—Report of 2 patients

Pembrolizumab reactivates pulmonary granulomatosis

B1a Lymphocytes (CD19+CD5+) Deficiency in Patients with Crohn’s Disease and Its Relation with Disease Severity

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