Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis

Table 4 Patient characteristic analysis according to blister fluid heat map clusters

Group by heat map clustering	Diffuse/limited patient	Disease duration (years)	Skin score	Antibodies	Current therapy	Past therapy	Current steroid
Group 1	DcSSc17	8	24	fs, RNApol	HCQ		No
Interleukin-6	DcSSc20	1	27	nuc	MMF		Yes
	DcSSc14	1	38	ACA	MMF		Yes
	DcSSc19	5	28	fs, U3RNP	HCQ	Campath1	No
	DcSSc16	2	34	hom, Scl70	MTX	CYC	Yes
	LcSSc6	3	6	ACA			No
	DcSSc15	5	35	hom, Scl70 + Ro	MMF		Yes
	DcSSc18	15	24	hom, Scl70	HCQ		No
Mean (SEM)		5 (1.7)	27 (3.5)
Group 2	LcSSc2	23	6	fs, Scl70 + Ro	HCQ, MMF		Yes
Interferon gamma	DcSSc1	10	16	crs, nRNP + Ro	MMF, MTX	CYC	Yes
	DcSSc9	33	28	nuc	AZA	MTX, MMF, CIC	Yes
	DcSSc4	11	30	hom, Scl70	MMF, IMI	AZA, CYC	No
	DcSSc6	6	24	fs, RNA pol	MMF, HCQ	CYC	Yes
	DcSSc7	13	9	nuc,	HCQ		No
	DcSSc11	2	34	hom, Scl70	MTX	CYC	Yes
	DcSSc2	8	8	hom, Scl70	HCQ	MMF	No
	DcSSc8	20	30	hom + nuc, Scl70			No
Mean (SEM)		14 (3.2)	21 (3.6)
Group 3	DcSSc10	3	12	nuc	IVIG	MMF	Yes
Quiescent	LcSSc1	6	4	ACA			No
	DcSSc3	8	15	fs, RNA pol	MTX	MMF	Yes
	DcSSc13	2	12	fs + cyto	MTX		Yes
	DcSSc5	20	10	hom, Scl70	MMF	CYC	Yes
	LcSSc5	12	15	fs			No
	DcSSc12	10	14	hom, Scl70	AZA	CYC	No
	LcSSc3	3	6	ACA			No
	LcSSc4	4	6	fs + nuc	MTX		Yes
Mean (SEM)		7.5 (1.9)	10 (1.4)

Patients were grouped according to blister fluid heat map cluster. Patients in Group 1 (interleukin-6 high, innate inflammatory) were more likely to have early DcSSc with high skin score, Group 2 (interferon gamma high, effector T cell) were mainly late stage DcSSc, and Group 3 (quiescent pattern) were more likely to be LcSSc or DcSSc with low skin scores. Analysis of variance showed significant difference for disease duration between groups (P = 0.042) and skin score (P = 0.003). Scheffe post hoc analysis showed higher skin score in Group 1 compared with Group 3 (P = 0.005), otherwise P = not significant. Pattern of anti-nuclear antibody staining: homogeneous (hom), fine speckled (fs), nucleolar (nuc), coarse speckled (crs), cytoplasmic pattern (cyto). Therapy: azathioprine (AZA), cyclophosphamide (CYC), cyclosporine (CIC), hydroxychloroquine (HCQ), intravenous immunoglobulin (IVIG), mycophenolate (MMF), methotrexate (MTX). ACA, anticentromere antibody; DcSSc, diffuse cutaneous systemic sclerosis; LcSSc, limited cutaneous systemic sclerosis; SEM, standard error of the mean.

ISSN: 1478-6362