Low-dose IL-2 therapy limits the reduction in absolute numbers of peripheral lymphocytes in systemic lupus erythematosus patients with infection

Figures & data

Table 1. Comparison of baseline characteristics between the non-infected group and infected group in patients with SLE.

Characteristics	Non-infected (n = 333)	Infected (n = 162)	p value
Age, years, mean (SD)	35.9 (14.0)	39.0 (15.8)	.025
Female, n (%)	302 (90.1)	144 (18)	.525
Duration of SLE, years, median (range)	3.0 (0.02–34.0)	4.0 (0.03–39.9)	.098
WBC, ×10^9/L, mean (SD)	5.49 (2.98)	5.34 (3.42)	.611
Platelet, ×10^12/L, mean (SD)	188 (82)	158 (94)	.001
Lymphocyte, ×10^9/L, mean (SD)	1.35 (0.69)	1.06 (0.66)	.601
Neutrophil, ×10^9/L, mean (SD)	3.80 (2.84)	3.95 (3.06)	<.001
Prednisone dose, mg/day, median (range)	30 (0, 60)	40 (0, 60)	.008
Use of concomitant agents (no. of patients)
Hydroxychloroquine	251	112	—
Methotrexate	38	11	—
Leflunomide	73	24	—
Cyclophsphamide	158	67	—
Mycophenolate mofetil	69	33	—

Table 2. Localization and cause of infection (n = 162).

	N	%
Localization
Respiratory	116	71.6
Gastrointestinal	30	18.5
Urinary tract	21	13
Others	18	11.1
Pathogens
Bacteria	97	59.9
Fungus	20	12.3
Virus	17	10.5
Unknown	33	20.4

Figure 1. Multiple subpopulations of lymphocytes decreased in peripheral blood of SLE patients with infection. Absolute numbers of peripheral lymphocytes subpopulations were analyzed by flow cytometry. Data were presented as mean ± SD and statistical analysis was determined by one-way ANOVA. *p <.05, **p <.01, ***p <.001. (a) SLE patients (n = 495) have lower levels of T, B, NK, CD4 + T, and CD8 + T cells in PB compared with healthy controls. The numbers of PB lymphocytes in the infected groups (n = 162) was also much lower than those in non-infected patients (n = 333). (b) Comparison of numbers of CD4 + T cell subsets among different groups. Patients with SLE had lower levels of Th1 cells, Th2 cells, Th17 cells, as well as Treg cells compared with healthy donors (n = 132), especially the infected groups.

Figure 2. Multiple subpopulations of peripheral lymphocytes of SLE patients were significantly upregulated after low-dose IL-2 treatment (n = 54). Absolute numbers of lymphocyte subpopulations in peripheral blood were analyzed by flow cytometry. (a–i) Changes in the numbers of T, B, NK, CD4 + T, CD8 + T, Th1, Th2, Th17, and Treg cells. Comparison between amounts of cells at baseline and after the treatment. Data were presented as mean ± SD and were calculated and compared by paired-sample t-test. *p <.05, **p <.01, ***p <.001.

Figure 3. Lymphocyte subpopulations in patients with SLE (n = 54) were upregulated by IL-2 treatment and got to levels near healthy controls (n = 132). Absolute numbers of lymphocyte subpopulations in peripheral blood were analyzed by flow cytometry. Data were presented as mean ± SD and statistical analysis was determined by one-way ANOVA. *p <.05, ***p <.001. (a) SLE patients had a comparable level of T, B, CD4 + T, and CD8 + T cells in PB to healthy controls. (b) Comparison of the number of CD4 + T cell subsets among different groups. Patients with SLE had a comparable number of Th1, Th2, and Th17, and even higher Treg cells than healthy donors, especially the infected groups.

Table 3. Comparison of the number of PB lymphocyte subpopulations in patients with SLE before and after IL-2 treatment (n = 54).

	Without infection (n = 41)			With infection (n = 13)
	Before	After	p value	Before	After	p value
T, cells/μl, mean (SD)	911.4 (508.1)	1,334.6 (760.4)	<.001	493.9 (349.2)	760.7 (545.1)	.042
B, cells/μl, mean (SD)	160.8 (134.5)	341.6 (324.5)	<.001	110.0 (120.9)	182.9 (267.1)	.207
CD4 + T, cells/μl, mean (SD)	454.8 (274.9)	657.8 (368)	.003	228.6 (219.2)	327.5 (224.6)	.097
CD8 + T, cells/μl, mean (SD)	419.3 (234.5)	618.7 (416.1)	<.001	242.3 (144.3)	406.4 (322.4)	.044
NK, cells/μl, mean (SD)	94.3 (91.9)	115.4 (126.1)	.199	50.3 (31.5)	67.7 (45.1)	.205
Th1, cells/μl, mean (SD)	51.7 (44)	86.9 (87.5)	.007	34.9 (30.0)	54.2 (43.4)	.120
Th2, cells/μl, mean (SD)	10.2 (8.7)	13.2 (11.7)	.144	5.4 (6.7)	8.1 (10.2)	.424
Th17, cells/μl, mean (SD)	8.5 (6.6)	15.3 (21.4)	.050	4.0 (3.8)	7.8 (5.9)	.041
Treg, cells/μl, mean (SD)	28.0 (33.0)	80.0 (50.0)	<.001	9.1 (7.8)	34.8 (32.1)	.005

The lymphocyte subpopulations of the patients were compared respectably. p value <.05 was considered statistically significant.

Abbreviation: PB, peripheral blood.

Table 4. Comparison of peripheral lymphocyte subsets in patients with SLE before and after IL-2 treatment (mean ± SD).

Characteristics, cells/μl	Before (n = 54)	After (n = 54)	t	p
T	810.907 ± 504.871	1,196.463 ± 751.697	4.539	<.001
B	148.565 ± 132.061	303.366 ± 316.717	3.992	<.001
CD4 + T	400.318 ± 278.241	578.319 ± 366.027	3.564	.001
CD8 + T	376.683 ± 228.111	567.607 ± 403.275	4.807	<.001
NK	83.694 ± 83.409	103.908 ± 113.545	1.603	.115
Th1	47.668 ± 41.421	79.066 ± 80.022	3.195	.002
Th2	9.042 ± 8.435	11.946 ± 11.484	1.720	.091
Th17	7.435 ± 6.321	13.527 ± 19.071	2.357	.022
Treg	13.832 ± 19.141	69.098 ± 50.018	8.940	<.001

Table 5. Comparison of peripheral lymphocyte subsets in patients with SLE after IL-2 treatment and HCs (mean ± SD).

Characteristics, cells/μl	HCs (n = 132)	After (n = 54)	t	p
T	1,335.345 ± 332.566	1,196.463 ± 751.697	1.306	.196
B	205.252 ± 81.324	303.366 ± 316.717	‒2.246	.029
CD4 + T	712.159 ± 203.548	578.319 ± 366.027	2.532	.014
CD8 + T	485.889 ± 199.919	567.607 ± 403.275	‒1.419	.161
NK	297.961 ± 134.334	103.908 ± 113.545	10.015	<.001
Th1	96.367 ± 69.859	79.066 ± 80.022	1.468	.144
Th2	10.588 ± 5.995	11.946 ± 11.484	‒.824	.413
Th17	7.645 ± 4.052	13.527 ± 19.071	‒2.246	.029
Treg	34.133 ± 12.663	69.098 ± 50.018	‒5.071	<.001

Table 6. Comparison of baseline characteristics in patients with SLE before and after IL-2 treatment.

Characteristics	Before	After	p value
Blood routine (n = 48)
WBC, ×10^9/L, mean (SD)	4.08 (2.70)	8.45 (4.47)	<.001
Platelet, ×10^12/L, mean (SD)	158 (85)	191 (90)	.017
Lymphocyte, ×10^9/L, mean (SD)	1.12 (.63)	2.09 (1.18)	<.001
Neutrophil, ×10^9/L, mean (SD)	3.49 (2.59)	5.87 (3.90)	<.001
Complement (n = 18)
C3, mean (SD)	.51 (.20)	.55 (.23)	.373
C4, mean (SD)	.10 (.07)	.11 (.13)	.558
ESR, mm/h, mean (SD) (n = 42)	45.69 (36.78)	24.24 (23.85)	<.001
CRP, mg/dL, mean (SD) (n = 20)	10.18 (16.56)	8.14 (10.35)	.584

Abbreviations: ESR, erythrocyte sedimentation rate; CRP, C-reaction protein.

Data availability statement

All data generated or analyzed during this study are included in this published article.