Systemic inflammatory immune signatures in a patient with CRB1 linked retinal dystrophy.
BACKGROUND
In this report we describe, for the first time, the activation of the peripheral immune compartment in a patient with a CRB1 linked retinal degenerative disease, masquerading as intermediate uveitis.


METHODS
To monitor the immune system during systemic immunosuppressive treatment, given for the initial diagnosis of intermediate uveitis, blood samples were taken before and during therapy, for analysis of peripheral blood mononuclear cell-subsets and circulating immune mediators.


RESULTS
The levels of various pro-inflammatory immune mediators (including MIF, TSLP, CCL2/MCP-1, CXCL9, CXCL10, IFN-β, IL-6, IL-17, IL-21, IL-22, and IL-23) were elevated in serum at the first time point, and decreased under immunosuppressive treatment. In parallel, the frequency of activated (CD86+) CD1c+ myeloid dendritic cells in blood was proportional to the central foveal thickness measured by optical coherence tomography.


CONCLUSIONS
These observations challenge the current view on the distinct pathophysiology of retinal degenerative and retinal inflammatory conditions in this patient.
a Department of Ophthalmology , University Medical Centre Utrecht , Utrecht , The Netherlands.|b Laboratory of Translational Immunology , University Medical Centre Utrecht , Utrecht , The Netherlands.
Fleurieke
F
Verhagen
a Department of Ophthalmology , University Medical Centre Utrecht , Utrecht , The Netherlands.|b Laboratory of Translational Immunology , University Medical Centre Utrecht , Utrecht , The Netherlands.
Jonas
J
Kuiper
c U-DAIR , University Medical Center Utrecht , Utrecht , The Netherlands.
Stefan
S
Nierkens
a Department of Ophthalmology , University Medical Centre Utrecht , Utrecht , The Netherlands.
Saskia M
SM
Imhof
b Laboratory of Translational Immunology , University Medical Centre Utrecht , Utrecht , The Netherlands.
Timothy
T
Radstake
a Department of Ophthalmology , University Medical Centre Utrecht , Utrecht , The Netherlands.
Joke
J
de Boer
D000293:Adolescent; D018949:Antigens, CD1 / Q000378:metabolism; D016207:Cytokines / Q000097:blood; D003713:Dendritic Cells / Q000276:immunology*; D003937:Diagnosis, Differential; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D018836:Inflammation Mediators / Q000097:blood; D008269:Macular Edema / Q000175:diagnosis / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012160:Retina / Q000473:pathology / Q000502:physiology*; D015867:Uveitis, Intermediate / Q000175:diagnosis
D018949:Antigens, CD1; C437944:CD1C protein, human; C448939:CRB1 protein, human; D016207:Cytokines; D005136:Eye Proteins; D006023:Glycoproteins; D018836:Inflammation Mediators; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins
CRB1 mutation; Retinal degenerative disease; cytokine analysis; flow cytometry; uveitis