scholarly journals Conjunctival Matrix Metalloproteinase-9 Clinical Assessment in Early Ocular Graft versus Host Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Luigi Berchicci ◽  
Emanuela Aragona ◽  
Alessandro Arrigo ◽  
Alessandro Marchese ◽  
Elisabetta Miserocchi ◽  
...  
Keyword(s):  
T Cell ◽  
Matrix Metalloproteinase ◽  
Graft Versus Host Disease ◽  
Ocular Surface ◽  
Matrix Metalloproteinase 9 ◽  
Schirmer Test ◽  
Host Disease ◽  
Graft Versus Host ◽  
Early Stages ◽  
Metalloproteinase 9

Purpose. Graft versus Host Disease (GVHD) typically affects the ocular surface, with a presentation resembling Dry Eye Disease (DED). Although the etiopathology is not completely known, the conjunctiva might be a key site of T-cell activation. The differential diagnosis might be tricky at early stages, because of the lack of dedicated clinical and laboratory tests. To meet these needs, we evaluated the suitability of ocular surface matrix metalloproteinase-9 (MMP-9) clinical test. Methods. Consecutive GVHD patients, referred to IRCCS San Raffaele Scientific Institute, were recruited. DED patients served as controls. MMP-9 was tested through InflammaDry immunoassay kit in both groups; Ocular Surface Disease Index (OSDI) questionnaire, tear osmolarity, fluorescein Tear Break-up Time (TBUT), corneal and conjunctival staining, and Schirmer test I were also collected. Parametric and nonparametric statistical tests were used to analyze the intergroup differences; Receiver Operating Characteristics (ROC) curve analysis was carried out to perform sensitivity and specificity evaluations. Results. Forty-five GVHD and 40 DED patients were included. MMP-9 expression was significantly higher in GVHD group than in DED (84.4% vs 33%, p ≤ 0.001 ). Corneal and conjunctival staining scores resulted worse in GVHD than in DED (0.95 ± 1.16 vs 0.40 ± 0.63, p = 0.02 ; 0.77 ± 0.42 vs 0.40 ± 0.49, p = 0.0005 , respectively). No significant differences regarded the other collected parameters. GVHD group was characterized by positive correlations between MMP-9 and conjunctival staining (rho = 0.55, p = 0.0002 ) and between MMP-9 and OSDI (rho = 0.3, p = 0.01 ); a faint inverse correlation was found between MMP-9 and Schirmer test (rho = −0.25, p = 0.04 ). Conclusion. MMP-9 has a role in physiologic cellular remodeling; when a proinflammatory stimulus occurs, MMP-9 molecules are overreleased in the extracellular matrix. The positive expression of MMP-9 in GVHD may be interpreted as the consequence of a T-cell aggression against self-antigens and may be considered a reliable biomarker to detect ocular surface inflammation in GVHD, even in early stages of the disease.

scholarly journals Simultaneous colonic T-cell lymphoma and graft-versus-host disease: A rare diagnosis

2021 ◽  
Vol 24 ◽  
pp. 200507
Author(s):  
Savanah D. Gisriel ◽  
Kenneth W. Hung ◽  
Demetrios T. Braddock ◽  
Stuart Seropian ◽  
Francine M. Foss ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Host Disease ◽  
Graft Versus Host ◽  
Rare Diagnosis

scholarly journals The DC-HIL ligand syndecan-4 is a negative regulator of T-cell allo-reactivity responsible for graft-versus-host disease

Immunology ◽  
2013 ◽  
Vol 138 (2) ◽  
pp. 173-182 ◽  
Author(s):  
Jin-Sung Chung ◽  
Mizuki Tomihari ◽  
Kyoichi Tamura ◽  
Tetsuhito Kojima ◽  
Ponciano D. Cruz ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Negative Regulator ◽  
Host Disease ◽  
Graft Versus Host

scholarly journals Identification of amplified clonal T cell populations in the blood of patients with chronic graft-versus-host disease: positive correlation with response to photopheresis

2002 ◽  
Vol 30 (8) ◽  
pp. 509-515 ◽  
Author(s):  
LE French ◽  
T Alcindor ◽  
M Shapiro ◽  
KS McGinnis ◽  
DJ Margolis ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Cell Populations ◽  
Host Disease ◽  
Positive Correlation ◽  
Graft Versus Host

scholarly journals Aberrant regulation of superantigen responses during T-cell reconstitution and graft-versus-host disease in immunodeficient mice

Blood ◽  
2002 ◽  
Vol 100 (6) ◽  
pp. 2216-2224
Author(s):  
David Spaner ◽  
Xiaofang Sheng-Tanner ◽  
Andre C. Schuh
Keyword(s):  
T Cells ◽  
T Cell ◽  
Graft Versus Host Disease ◽  
Adoptive Transfer ◽  
Scid Mice ◽  
Control Mechanisms ◽  
Activated T Cells ◽  
Host Disease ◽  
Immunodeficient Mice ◽  
Graft Versus Host

Acute graft-versus-host disease (GVHD) after allogeneic stem cell transplantation is associated with impaired deletion and anergy of host-reactive T cells. To elucidate the immunoregulatory events that may contribute to such dysregulated T-cell responses in GVHD, we studied superantigen (SAg) responses after adoptive T-cell transfer into severe combined immunodeficient (SCID) mice. SAg responses are normally regulated by mechanisms involving deletion and anergy, with SAg-reactive T cells typically being deleted rapidly in vivo. In a SCID mouse model of GVHD, however, allogeneic host SAg-reactive T cells were not deleted rapidly, but rather persisted in increased numbers for several months. Moreover, depending on the timing of SAg stimulation and the numbers of T cells transferred, dysregulation (impaired deletion and anergy) of SAg responses could be demonstrated following the adoptive transfer of syngeneic T cells into SCID mice as well. Transgenic T-cell receptor-bearing KJ1-26.1+ T cells were then used to determine the fate of weakly reactive T cells after adoptive transfer and SAg stimulation. When transferred alone, KJ1-26.1+ T cells demonstrated impaired deletion and anergy. In the presence of more strongly staphylococcal enterotoxin B (SEB)–reactive T cells, however, KJ1-26.1+ T cells were regulated normally, in a manner that could be prevented by inhibiting the effects of more strongly SEB-reactive cells or by increasing the level of activation of the KJ1-26.1+ T cells themselves. We suggest that the control mechanisms that normally regulate strongly activated T cells in immunocompetent animals are lost following adoptive transfer into immunodeficient hosts, and that this impairment contributes to the development of GVHD.

scholarly journals In vivo T-cell clonal amplification at time of acute graft-versus-host disease

Blood ◽  
1994 ◽  
Vol 84 (8) ◽  
pp. 2815-2820 ◽  
Author(s):  
PY Dietrich ◽  
A Caignard ◽  
A Lim ◽  
V Chung ◽  
JL Pico ◽  
...  
Keyword(s):  
T Cell ◽  
Graft Versus Host Disease ◽  
Donor Blood ◽  
Host Disease ◽  
Graft Versus Host ◽  
Junctional Region ◽  
Run Off ◽  
Pcr Products ◽  
Acute Graft

In a series of patients transplanted with HLA-matched allogeneic bone marrow grafts (alloBMT), we previously showed that a few T-cell receptor (TCR) V alpha and V beta gene segment transcripts were overexpressed in skin compared with blood at the time of acute graft- versus-host disease (aGVHD). Here, in one selected patient with overexpressed V beta 16 and V alpha 11 transcripts in skin, we analyzed the junctional variability of these transcripts in donor blood, patient blood, and skin collected at aGVHD onset. A unique junctional region sequence accounted for 81% of in frame V beta 16 transcripts (13 of 16) in skin and 59% (13 of 22) in patient blood. Similarly, two recurrent junctional region sequences were found in skin V alpha 11 transcripts, one accounting for 66% (21 of 32) and the other for 16% (5 of 32). These recurrences were also found in patient blood (36% and 15% of V alpha 11 transcripts, respectively). To extend our analysis, a polymerase chain reaction (PCR)-based method was used to precisely determine TCR beta transcript length in run-off reactions using uncloned bulk cDNA samples. All V beta-C beta PCR products analyzed in donor blood, as well as the majority of those analyzed in patient blood, included transcripts with highly diverse junctional region sizes. As expected from the sequence data, most V beta 16-C beta PCR products in skin and patient blood were of the same size (ie, same junctional region). In addition, V beta 3, V beta 5, and V beta 17 transcripts in skin were shown to display highly restricted size variability. The clonality of the V beta 16-C beta and V beta 17-C beta transcripts was further supported by the results of run-off reactions using 13 J beta specific primers. We have identified several recurrent TCR transcripts in skin, some of them also present in patient blood. These data support the view that several T-cell subpopulations are clonally expanded in vivo at the time of aGVHD onset in this case of related HLA-matched alloBMT.

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