scholarly journals In Vivo Reflectance Confocal Microscopy in the Early Diagnosis of Acute Cutaneous Graft-Versus-Host Disease: A Pilot Study

2012 ◽  
Vol 18 (2) ◽  
pp. S369
Author(s):  
J.M. Corbin ◽  
A. MacDonald ◽  
K.S. Purdy ◽  
A. Webb ◽  
S. Pasternak ◽  
...  
Keyword(s):  
Pilot Study ◽  
Confocal Microscopy ◽  
Early Diagnosis ◽  
Graft Versus Host Disease ◽  
Reflectance Confocal Microscopy ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Features of cutaneous acute graft‐versus‐host disease by reflectance confocal microscopy

2019 ◽  
Vol 181 (4) ◽  
pp. 829-831 ◽  
Author(s):  
I. Saknite ◽  
M. Gill ◽  
C. Alessi‐Fox ◽  
M. Byrne ◽  
M. Jagasia ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Graft Versus Host Disease ◽  
Reflectance Confocal Microscopy ◽  
Host Disease ◽  
Graft Versus Host ◽  
Acute Graft

Corneal features in ocular graft-versus-host disease by in vivo confocal microscopy

2017 ◽  
Vol 255 (12) ◽  
pp. 2389-2397 ◽  
Author(s):  
Tudor C. Tepelus ◽  
Gloria B. Chiu ◽  
Jyotsna Maram ◽  
Jianyan Huang ◽  
Vikas Chopra ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Graft Versus Host Disease ◽  
In Vivo Confocal Microscopy ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Observation of Chronic Graft-Versus-Host Disease Mouse Model Cornea with In Vivo Confocal Microscopy

Diagnostics ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1515
Author(s):  
Shota Shimizu ◽  
Shinri Sato ◽  
Hiroko Taniguchi ◽  
Eisuke Shimizu ◽  
Jingliang He ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Mouse Model ◽  
Graft Versus Host Disease ◽  
Pathological Condition ◽  
Inflammatory Cells ◽  
In Vivo Confocal Microscopy ◽  
Host Disease ◽  
Epithelial Damage ◽  
Graft Versus Host

Graft-versus-host disease (GVHD) is a major complication after hematopoietic stem cell transplantation (HSCT), and ocular GVHD can cause severe dry eye disease that can lead to visual impairment. Epithelial damage, vascular invasion, corneal fibrosis, and corneal perforation may occur in severe cases. It is generally accepted that inflammatory cells such as dendritic cells and T cells contribute to this pathological condition. However, it is still unknown what pathological condition occurs on the ocular surface after HSCT, and when. We therefore observed the dynamics of inflammatory cells in the cornea of chronic GVHD (cGVHD) model mice from 1 to 4 weeks after bone marrow transplantation (BMT) by in vivo confocal microscopy (IVCM) and considered the relationship with the pathophysiology of ocular GVHD (tear volume, corneal epithelial damage). In the allogeneic group, neovascularization occurred in all eyes at 1 week after BMT, although almost all vessels disappeared at 2 weeks after BMT. In addition, we revealed that infiltration of globular cells, and tortuosity and branching of nerves in the cornea occurred in both cGVHD mice and human cGVHD patients. Thus, we consider that cGVHD mouse model study by IVCM reproduces the state of ocular GVHD and may contribute to elucidating the pathological mechanism for ocular GVHD.

scholarly journals Real-Time Reflectance Confocal Microscopy Features of Cutaneous Graft-Versus-Host Disease

2021 ◽  
Vol 27 (3) ◽  
pp. S294-S295
Author(s):  
Rachel Reingold ◽  
Joseph R. Stoll ◽  
Jilliana Monnier ◽  
Camila Pena ◽  
Japbani Nanda ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Real Time ◽  
Graft Versus Host Disease ◽  
Reflectance Confocal Microscopy ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Key Histopathology Features of Cutaneous Acute Graft-Versus-Host Disease Can be Detected Noninvasively

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3278-3278
Author(s):  
Inga Saknite ◽  
Melissa Gill ◽  
Alessi-Fox Christi ◽  
Jeffrey P Zwerner ◽  
Julia S Lehman ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Graft Versus Host Disease ◽  
Research Funding ◽  
Vertical Section ◽  
Reflectance Confocal Microscopy ◽  
Drug Reactions ◽  
Host Disease ◽  
Graft Versus Host ◽  
Interrater Variability ◽  
Acute Graft

BACKGROUND. Cutaneous erythema and histopathology features in patients post allogeneic hematopoietic cell transplantation (HCT) are nonspecific, making it difficult to distinguish acute graft-versus-host disease (aGVHD) from engraftment syndrome, drug reactions, viral infections, and other etiologies. Biopsies from different locations on the same patient frequently differ in aGVHD grade, and serial biopsies of a single lesion are not possible. Proper biopsy site selection, timing, and serial noninvasive microscopic monitoring may improve our understanding and management of aGVHD. In this study, we tested the feasibility of noninvasive reflectance confocal microscopy (RCM) to detect key histopathology features of cutaneous aGVHD. STUDY POPULATION. We enrolled 11 patients with high clinical suspicion of cutaneous aGVHD, as determined by a transplant physician. In total, 16 lesions of cutaneous aGVHD-affected site were imaged by RCM (6x6 mm2en face images at four different depths) and subsequently biopsied (4x4 mm punch biopsy). 9 out of 11 patients had only skin involvement, and 2 patients had skin and gut aGVHD. 5 patients had >50% body surface area (BSA) affected, 1 had 18-50% BSA, and 5 had <18% BSA. 8 out of 11 patients required systemic corticosteroids and 3 patients received topical corticosteroids. All patients were imaged before starting treatment. METHODS. We used a clinical confocal microscope (Vivascope 1500, Caliber I.D.), which enables real-time evaluation of epidermal and superficial dermal tissue at sub-cellular resolution. Four reflectance confocal microscopists blinded to histopathology independently evaluated the presence or absence of 18 RCM features1. Concurrently, four dermatopathologists blinded to clinical and confocal information determined the presence or absence of 19 histopathology features, as well as the Lerner aGVHD grade. A histologic feature was determined as "present" in a lesion when marked by most experts (expert vote) or resolved by a fifth expert in case of a disagreement among four experts. The reflectance confocal microscopist vote was then correlated to the dermatopathologist expert vote for 17 overlapping features. We also evaluated the interrater variability among microscopists and among dermatopathologists. RESULTS. The main aGVHD features by Lerner grade had > 88% correlation between RCM and histopathology: (1) basal vacuolar change, (2) presence of dyskeratotic keratinocytes, and (3) dermal inflammation. By contrast, dyskeratotic cells and inflammation at the adnexal structures had <50% correlation. This may be attributed to the fact that more adnexal structures are typically visible in the 6x6 mm2 RCM horizontal tissue view compared to vertical section histopathology. We found a similar interrater variability among RCM experts (70%) and dermatopathologists (68%). CONCLUSIONS. In this pilot study, we show that noninvasive label-free RCM of skin enables detection of the main Lerner grade features of cutaneous aGVHD. We found a similar interrater variability among reflectance confocal microscopists and among dermatopathologists who each independently evaluated the presence or absence of a list of aGVHD features. Future studies can build on this work to evaluate the feasibility of RCM to determine cutaneous aGVHD grade, as well as distinguish between rash due to aGVHD and drug reactions. ACKNOWLEDGEMENT. This work was supported in part by Career Development Award Number IK2 CX001785 from the United Sates Department of Veterans Affairs Clinical Science R&D (CSRD) Service. Saknite I, Gill M, Alessi-Fox C, Byrne M, Jagasia M, Gonzalez S, Ardigo M, Tkaczyk ER. Features of cutaneous acute graft-versus-host disease by reflectance confocal microscopy. Br J Dermatol (2019). Disclosures Christi: Caliber I.D.: Employment, Equity Ownership. Byrne:Karyopharm: Research Funding. Jagasia:Kadmon: Consultancy; Incyte: Consultancy; Janssen: Research Funding. Tkaczyk:Incyte: Consultancy.

scholarly journals Granzyme B is not required for regulatory T cell–mediated suppression of graft-versus-host disease

Blood ◽  
2010 ◽  
Vol 115 (9) ◽  
pp. 1669-1677 ◽  
Author(s):  
Sheng F. Cai ◽  
Xuefang Cao ◽  
Anjum Hassan ◽  
Todd A. Fehniger ◽  
Timothy J. Ley
Keyword(s):  
Immune Responses ◽  
Treg Cell ◽  
Graft Versus Host Disease ◽  
Granzyme B ◽  
Target Organ Damage ◽  
Organ Damage ◽  
Treg Cells ◽  
Host Disease ◽  
Graft Versus Host

Abstract Regulatory T (Treg) cells can suppress a wide variety of immune responses, including antitumor and alloimmune responses. The mechanisms by which Treg cells mediate their suppressive effects depend on the context of their activation. We previously reported that granzyme B is important for Treg cell–mediated suppression of antitumor immune responses. We therefore hypothesized that granzyme B may likewise be important for suppression of graft-versus-host disease (GVHD). We found that allogeneic mismatch induces the expression of granzyme B in mixed lymphocyte reactions and in a model of graft-versus-host disease (GVHD). However, wild-type and granzyme B–deficient Treg cells were equally able to suppress effector T (Teff) cell proliferation driven by multiple stimuli, including allogeneicantigen-presenting cells. Surprisingly, adoptive transfer of granzyme B–deficient Treg cells prevented GVHD lethality, suppressed serum cytokine production in vivo, and prevented target organ damage. These data contrast strikingly with our previous study, which demonstrated that granzyme B plays a nonredundant role in Treg cell–mediated suppression of antitumor responses. Taken together, these findings suggest that targeting specific Treg cell–suppressive mechanisms, such as granzyme B, may be therapeutically beneficial for segregating GVHD and graft-versus-tumor immune responses.

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