Elevation of CD16⁺CD56⁺ NK-cells and down-regulation of serum interleukin-21 (IL-21) and IL-1α after splenectomy in relapsed hemophagocytic lymphohistiocytosis of unknown cause

Figures & data

Table 1. Clinical characteristics of 29 patients with relapsed HLH of unknown cause.

Clinical manifestation	n	%
Clinical symptoms
Fever	29	100.0
Splenomegaly	27	93.1
Lab tests
≥2 lines of blood cell↓	29	100.0
Ferritin ≥ 500 μg/l	26	89.7
Fgb < 1.5 g/l	19	65.5
TG > 3 mmol/l	8	27.6
Soluble CD25↑	27	93.1
Hemophagocytosis	14	48.3
Treatment regimen before splenectomy
HLH-94/HLH-04	11	37.9
DEP	4	13.8
E-CHOP/E-COP	13	44.8
Other	1	3.4
Improvement before splenectomy
PR	20	69.0
NR	9	31.0

Table 2. Changes in lymphocyte subpopulations and NK cell activity at different time-points before and after splenectomy.

Lymphocytes	Initial visit	BS	2 wk AS	24 wk AS
CD3^+ T cells (%)	82 (48–93)	84 (63–98)	80 (77–94)	76.5 (55–85)
P	0.683		0.208	0.139
CD4^+ T cells (%)	41.5 (13–78)	43 (13–62)	32.5 (19–58)	31 (13–63)
P	0.683		0.401	0.102
CD8^+ T cells (%)	41 (17–60)	42(19–70)	48.5 (30–65)	39.5 (30–60)
P	0.308		0.463	0.683
CD4^+/CD8^+ ratio	1 (0.24–4.59)	1(0.22–3.26)	0.68 (0.31–2.1)	0.695 (0.35–1.29)
P	0.646		0.14	0.214
CD19^+ B cells (%)	7 (1–49)	4 (0–16)	2 (0–22)	1 (0–32)
P	0.113		0.262	0.324
CD16^+CD56^+ NK cells (%)	4 (0–15)	8 (0–27)	8.5 (2–20)	15.1 (10–21)
P	0.08		0.054	0.003
NK cell activity (%)	13.81 (9.57–17.16)	13.4 (10.7–18.38)	17.46 (14.16–25.34)	19.7 (11.8–28.5)
P	0.866		0.068	0.028

BS: before splenectomy; AS: after splenectomy.

Table 3. Changes in cytokines before and after splenectomy in 7 HLH patients.

Cytokine	BS (pg/ml)	4 wk AS (pg/ml)	P-value
IFN-γ	398.67 (36.19–983.17)	192.43 (0.94–783.77)	0.237
IL-6	58.22 (34.15–293.16)	22.15 (10.49–113.75)	0.109
TNF-α	45.3 (9.68–175.59)	49.1 (1.94–81.35)	0.31
IL-21	14.58(6.98–34.33)	10.21(0–11.99)	0.028
IL-1α	2.41(1.3–3.7)	1.27(0.23–1.92)	0.018

Table 4. IFN-γ levels and treatment effectiveness before and after splenectomy in seven HLH patients.

Case	Sex	Age (y)	Condition BS	Condition AS	IFN-r (BS, pg/ml)	IFN-r (4 wk AS, pg/ml)
1	F	41	PR	CR	36.19	0.94
2	F	7	PR	PR	710.04	192.43
3	F	54	NR	NR	398.67	491.01
4	F	51	PR	CR	410.11	14.12
5	F	27	PR	PR	983.17	783.77
6	M	27	PR	NR	156.28	695.77
7	F	17	PR	PR	147.28	17.03

BS: before splenectomy; AS: after splenectomy.

Figure 1. Survival time of patients with relapsed HLH of unknown cause. (a) Comparison of total survival between the patients (PR + NR) with relapsed HLH of unknown cause who were treated with splenectomy vs. or those not treated with splenectomy. (b) Comparison of total survival between the patients (PR) with relapsed HLH of unknown cause who were treated with splenectomy vs. those not treated with splenectomy. (c) Comparison of total survival between the patients (NR) with relapsed HLH of unknown cause who were treated with splenectomy vs. those not treated with splenectomy.