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2017 ; 19
(1
): 136
Nephropedia Template TP
Lintermans LL
; Rutgers A
; Stegeman CA
; Heeringa P
; Abdulahad WH
Arthritis Res Ther
2017[Jun]; 19
(1
): 136
PMID28615072
show ga
BACKGROUND: Persistent expansion of circulating CD4(+) effector memory T cells
(T(EM)) in patients with granulomatosis with polyangiitis (GPA) suggests their
fundamental role in disease pathogenesis. Recent studies have shown that distinct
functional CD4(+) T(EM) cell subsets can be identified based on expression
patterns of chemokine receptors. The current study aimed to determine different
CD4(+) T(EM) cell subsets based on chemokine receptor expression in peripheral
blood of GPA patients. Identification of particular circulating CD4(+) T(EM)
cells subsets may reveal distinct contributions of specific CD4(+) T(EM) subsets
to the disease pathogenesis in GPA. METHOD: Peripheral blood of 63 GPA patients
in remission and 42 age- and sex-matched healthy controls was stained immediately
after blood withdrawal with fluorochrome-conjugated antibodies for cell surface
markers (CD3, CD4, CD45RO) and chemokine receptors (CCR4, CCR6, CCR7, CRTh2,
CXCR3) followed by flow cytometry analysis. CD4(+) T(EM) memory cells
(CD3(+)CD4(+)CD45RO(+)CCR7(-)) were gated, and the expression patterns of
chemokine receptors CXCR3(+)CCR4(-)CCR6(-)CRTh2(-),
CXCR3(-)CCR4(+)CCR6(-)CRTh2(+), CXCR3(-)CCR4(+)CCR6(+)CRTh2(-), and
CXCR3(+)CCR4(-)CCR6(+)CRTh2(-) were used to distinguish T(EM)1, T(EM)2, T(EM)17,
and T(EM)17.1 cells, respectively. RESULTS: The percentage of CD4(+) T(EM) cells
was significantly increased in GPA patients in remission compared to HCs.
Chemokine receptor co-expression analysis within the CD4(+) T(EM) cell population
demonstrated a significant increase in the proportion of T(EM)17 cells with a
concomitant significant decrease in the T(EM)1 cells in GPA patients compared to
HC. The percentage of T(EM)17 cells correlated negatively with T(EM)1 cells in
GPA patients. Moreover, the circulating proportion of T(EM)17 cells showed a
positive correlation with the number of organs involved and an association with
the tendency to relapse in GPA patients. Interestingly, the aberrant distribution
of T(EM)1 and T(EM)17 cells is modulated in CMV- seropositive GPA patients.
CONCLUSIONS: Our data demonstrates the identification of different CD4(+) T(EM)
cell subsets in peripheral blood of GPA patients based on chemokine receptor
co-expression analysis. The aberrant balance between T(EM)1 and T(EM)17 cells in
remission GPA patients, showed to be associated with disease pathogenesis in
relation to organ involvement, and tendency to relapse.
|Adult
[MESH]
|Aged
[MESH]
|Aged, 80 and over
[MESH]
|Female
[MESH]
|Granulomatosis with Polyangiitis/*immunology
[MESH]