Pandemic H1N1 Influenza Vaccination Responses in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients

Ji Hun Kim; Han Na Choi; Si Hye Kim; Hwajeong Lee; Sung-Hoon Park; Seong-Kyu Kim; Jung-Yoon Choe; Hyun-Hee Kwon; Hee-Jin Cheong

doi:10.4078/jrd.2013.20.2.87

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Kim, Choi, Kim, Lee, Park, Kim, Choe, Kwon, and Cheong: Pandemic H1N1 Influenza Vaccination Responses in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients

Original Article

J Rheum Dis 2013;20(2):87-93.

Published online: 31 April 2013

DOI: https://doi.org/10.4078/jrd.2013.20.2.87

Pandemic H1N1 Influenza Vaccination Responses in Rheumatoid Arthritis and Systemic Lupus Erythematosus Patients

Ji Hun Kim¹, Han Na Choi¹, Si Hye Kim¹, Hwajeong Lee^1,², Sung-Hoon Park^1,², Seong-Kyu Kim^1,², Jung-Yoon Choe^1,², Hyun-Hee Kwon¹, Hee-Jin Cheong³

¹Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea

²Arthritis and Autoimmunity Reseasrch Center, Catholic University of Daegu, Daegu, Korea

³Department of Internal Medicine, Korea University School of Medicine, Seoul, Korea

Corresponding to : Jung-Yoon Choe, Department of Internal Medicine, Catholic University of Daegu School of Medicine, 3056-6, Daemyung 4-dong, Nam-gu, Daegu 705-718, Korea. E-mail : jychoe@cu.ac.kr

Received 25 September 20121 November 2012 Accepted 1 November 2012

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

We investigated the efficacy and safety of pandemic H1N1 vaccine in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) patients, and evaluated its correlation with serum cytokine level.

Methods

A total of 43 RA patients and 31 SLE patients were enrolled in the study and were compared with age, sex-matched 40 healthy controls (HC). The blood samples drawn from selected patients before vaccination and in post-vaccination at week 4 were assayed in one session to measure the titers of antibodies against haemagglutinin specific for influenza virus strains: A/California/7/2009 NYMC X-179A (H1N1). Serum IL17 and CXCL13 levels were measured in the same session by enzyme-linked im-munosorbent assay. The association of serum cytokine level with anti-influenza antibody titer and mean fold increase (MFI) was investigated. Each specific side effect after vaccination was monitored in both the patients and control groups.

Results

The geometric mean antibody titer (GMT) for pre- and post-vaccination at week 4 was not significantly different between RA and HC, SLE and HC. The seroconversion rate in HC and RA was not significantly different, whereas the seroprotection rate is significantly higher in HC (82.5%) than RA (55.8%) (p<0.05). MFI in HC, RA, SLE were 19.65, 6.00 and 6.06, which were significantly higher in HC. Serum IL17 level was 6.28±2.89 pg/mL and 7.56±3.34 pg/mL in pre-, post-vaccination SLE patients, 33.85±15.62 pg/mL and 38.04±18.60 pg/mL in RA patients and was significantly lower in SLE patients. Serum CXCL13 level was 518.73± 720.29 pg/mL and 431.53±601.23 pg/mL in pre-, post-vaccination SLE patients, which was significantly higher than HC (149.64±248.81 pg/mL and 147.36±213.92 pg/mL in each pre-, post-vaccination) and was not significantly different with the level of RA patients. In SLE patients, significant correlations were detected between cytokine level and post-vaccination antibody titer (r=0.22 p=0.026 between IL 17 and GMT; r=0.44, p<0.05 between CXCL13 and GMT).

Conclusion

The increase in post-vaccination antibody titer is weaker in both RA and SLE patients group than the HC group. Post-vaccination antibody titer was positively correlated with B lymphocyte chemoattractant and CXCL13 in SLE patients, but not in RA patients.

Keywords: H1N1, IL-17, CXCL 13, Rheumatoid arthritis, Lupus erythematosus

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Table 1.

Baseline characteristics of the study population

	Healthy control (n=40)	RA (n=43)	SLE (n=31)	p-value^∗
Sex, male/female	1/39	2/41	0/31
Age, years, mean (SD)	56.08 (13.08)	51.21 (11.27)	39.50 (9.95)	<0.05
DAS28, mean (SD)
Pre vaccination		3.02 (1.35)
Post vaccination		3.12 (1.26)
SLEDAI, mean (SD)
Pre vaccination			2.25 (4.22)
Post vaccination			2.25 (4.22)
Disease duration, years, mean (SD)		7.48 (6.40)	6.23 (3.91)

RA: rheumatoid arthritis, SLE: systemic lupus erythematosus.

^∗ ANOVA

Table 2.

Medication used by the participating patients

	RA (n=43)	SLE (n=31)
Methotrexate
No. (%) patients	30 (69.77)	3 (9.77)
Dosage, mean (SD) mg/week	11.32 (3.98)	12.54 (2.22)
Prednisone
No. (%) patients	31 (72.09)	27 (87.09)
Dosage, mean (SD) mg/day	3.46 (2.15)	4.53 (3.84)
TNF α blockers, no. (%) patients	3 (6.98)	None
Adalimumab	3 (6.98)
Infliximab	0
Etanercept	0
Hydroxychloroquine, no. (%) patients	12 (27.91)	26 (83.87)
Leflunomide	9 (20.93)	0
Azathioprine	4 (9.30)	6 (19.4)

RA: rheumatoid arthritis, SLE: systemic lupus erythematosus

Table 3.

Humoral response to anti-influenza vaccination in RA patients

	Healthy control	RA	p-value
GMT
Pre vaccination, mean (SD)	53.50 (118.77)	75.35 (204.35)	0.56^∗
Post vaccination mean (SD)	396.00 (429.89)	322.91 (853.56)	0.63^∗
Seroconversion rate, %	90	79.00	0.17^†
Seroprotection rate, %	82.50	55.80	0.009^†
MFI	19.65 (26.67)	6.00 (5.70)	0.003^∗

RA: rheumatoid arthritis, GMT: geometric mean titer, MFI: mean fold increase.

^∗ t test,

^† Chi-square test

Table 4.

Humoral response to anti-influenza vaccination in SLE patients

	Healthy control	SLE	p-value
GMT
Pre vaccination, mean (SD)	53.50 (118.77)	71.61 (113.46)	0.52^∗
Post vaccination, mean (SD)	396.00 (429.89)	349.03 (365.14)	0.49^∗
Seroconversion rate, %	90	96.77	0.27^†
Seroprotection rate, %	82.50	77.42	0.59^†
MFI, mean (SD)	19.65 (26.67)	6.06 (3.73)	0.003^∗

SLE: systemic lupus erythematosus, GMT: geometric mean titer, MFI: mean fold increase.

^∗ t test,

^† Chi-square test

Table 5.

Serum cytokine, chemokine profiles between groups

	Healthy control	RA	SLE	p-value^∗
IL-17, pg/mL, mean (SD)
Pre	34.31 (33.99)	33.85 (15.62)	6.28 (2.89)	<0.05
Post	33.11 (17.80)	38.04 (18.60)	7.56 (3.34)	<0.05
CXCL13, pg/mL, mean (SD)
Pre	149.64 (248.81)	519.80 (1,678.92)	518.73 (720.29)	0.25
Post	147.36 (213.92)	318.41 (1,241.80)	431.53 (601.23)	0.37

RA: rheumatoid arthritis, SLE: systemic lupus erythematosus.

^∗ ANOVA

Table 6.

Serum cytokine, chemokine profiles in pre and post-vaccination

	IL-17, pg/mL, mean(SD)		p-value^∗	CXCL13, pg/mL, mean(SD)		p-value^∗
	Pre	Post	p-value^∗	Pre	Post	p-value^∗
HC	34.31 (33.99)	33.11 (17.80)	0.741	149.64 (248.81)	147.36 (213.92)	0.951
RA	33.85 (15.62)	38.04 (18.60)	0.003	519.80 (1,678.92)	318.41 (1,241.80)	0.038
SLE	6.28 (2.89)	7.56 (3.34)	0.14	518.73 (720.29)	431.53 (601.23)	0.535

HC: Healthy control, RA: rheumatoid arthritis, SLE: systemic lupus erythematosus.

^∗ Paired t test

Table 7.

Correlation of serum cytokine level with post-vaccination humoral response in the patient group

	Correlation^∗	GMT	Seroconversion	Seroprotection	MFI
RA
IL-17	Coefficient	0.02	−0.10	−0.13	−0.15
	p-value	0.89	0.52	0.42	0.93
CXCL13	Coefficient	−0.06	0.21	−0.10	−0.14
	p-value	0.72	0.18	0.53	0.39
SLE
IL-17	Coefficient	0.22	0.01	−0.36	0.01
	p-value	0.26	0.98	0.63	0.95
CXCL13	Coefficient	0.44	−0.03	−0.07	0.22
	p-value	<0.05	0.90	0.72	0.27

RA: rheumatoid arthritis, SLE: systemic lupus erythematosus, GMT: geometric mean titer, MFI: mean fold increase.

^∗ Pearson's correlation

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