Background/Purpose:

Polymyositis (PM) and dermatomyositis (DM) muscle tissue is characterized by infiltrating T cells, macrophages and dendritic cells, as well as cytokines and chemokines. In addition, the muscle fibers express major histocompatibility complex (MHC) class I. Patients are treated with high doses of glucocorticoids in combination with additional immunosuppressive drugs. However, remaining signs of inflammation in the muscle tissue, such as T cells, MHC class I and cytokines, as well as sustained muscle impairment are common even after prolonged treatment.  Our aim was to investigate how the gene expression in pathways of inflammation and muscle remodeling is affected by immunosuppressive treatment in patients with PM and DM.

Methods:

Six newly diagnosed, untreated patients (2 PM/4 DM, 2 men/4 women) with biopsies from m.vastus lateralis before and after a median of 10 (8-16) months of immunosuppressive treatment were analyzed using microarray. 

Results: Alterations in a number of genes coding for immune responses and muscle tissue remodelling were observed. 

Affy accession #	Gene	Gene ID	Fold	P-value
Immune response
1554519_at	CD80	CD80	-2,2	0,034
210895_s_at	CD86	CD86	-2,6	0,013
222868_s_at	interleukin 18 binding protein	IL18BP	-1,9	0,032
206295_at	interleukin 18	IL18	-2,2	0,041
205992_s_at	interleukin 15	IL15	-1,5	0,027
216598_s_at	chemokine (C-C motif) ligand 2	CCL2	-5,9	0,004
1555759_a_at	chemokine (C-C motif) ligand 5	CCL5	-3,1	0,003
1405_i_at	chemokine (C-C motif) ligand 5	CCL5	-3,0	0,043
206978_at	chemokine (C-C motif) receptor 2	CCR2	-2,3	0,004
206991_s_at	chemokine (C-C motif) receptor 5	CCR5	-2,8	0,027
204533_at	chemokine (C-X-C motif) ligand 10	CXCL10	-5,6	0,020
210163_at	chemokine (C-X-C motif) ligand 11	CXCL11	-6,3	0,005
211122_s_at	chemokine (C-X-C motif) ligand 11	CXCL11	-5,6	0,015
215313_x_at	MHC class I, A	HLA-A	-1,1	0,012
211911_x_at	MHC class I, B	HLA-B	-1,7	0,010
208812_x_at	MHC class I, C	HLA-C	-2,6	0,013
211991_s_at	MHC class II, DP alpha 1	HLA-DPA1	-2,2	0,046
203290_at	MHC class II, DQ alpha 1	HLA-DQA1	-2,8	0,036
211656_x_at	MHC class II, DQ beta 1	HLA-DQB1	-2,2	0,038
209312_x_at	MHC class II, DR beta 3	HLA-DRB3	-1,7	0,027
204806_x_at	MHC class I, F	HLA-F	-2,4	0,018
Muscle structure
206891_at	actinin, alpha 3	ACTN3	3,4	0,037
200930_s_at	vinculin	VCL	1,9	0,022
207145_at	growth differentiation factor 8	MSTN	2,3	0,041
204802_at	Ras-related associated with diabetes	RRAD	-3,4	0,013
204560_at	FK506 binding protein 5	FKBP5	3,2	0,016
206394_at	myosin binding protein C, fast type	MYBPC2	1,9	0,031
206304_at	myosin binding protein H	MYBPH	-6,9	0,036
208148_at	myosin, heavy polypeptide 4	MYH4	2,2	0,020
202724_s_at	forkhead box O1A	FOXO1	2,2	0,033

Conclusion: This data indicates that transcriptional alterations in genes involved in muscle tissue structure are taking place during immunosuppressive treatment.  The treatment down-regulates the muscle inflammation to some extent but the local milieu might be accountable for the preserved expression of inflammatory cells and mediators seen in treated PM/DM patients.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-immunosuppressive-treatment-on-gene-expression-in-patients-with-polymyositis-and-dermatomyositis/