Cytokine and autoantibody patterns in acute liver failure

Figures & data

Table 1.  Correlation between IL-17 and other analytes in each patient category.

	ANA	Anti-MPO	IL-21	IL-6	IL-2	Eotaxin	IL-4	IL-5	TNF-α	GM-CSF	IFN-γ
APAP	ns	ns	ns	ns	ns	ns	ns	ns	ns	ns	***
IDILI	ns	ns	ns	ns	***	*	ns	ns	*	*	***
HAV	ns	ns	ns	ns	**	ns	ns	ns	ns	ns	**
HBV	ns	ns	ns	**	***	ns	ns	ns	ns	ns	**
HCV	ns	ns	ns	**	ns	ns	ns	*	ns	ns	ns

Table

	IL-10	IL-12 (p40)	IL-13	IL-15	IL-1α	IL-1β	IL-3	IL-7	IL-8	IP-10	MCP-1	MIP-1α
APAP	ns	ns	ns	ns	ns	ns	ns	ns	ns	ns	ns	**
IDILI	ns	***	***	***	***	***	*	**	*	ns	ns	ns
HAV	ns	ns	ns	*	ns	ns	ns	ns	ns	ns	ns	*
HBV	*	ns	**	ns	ns	ns	ns	ns	ns	ns	*	*
HCV	ns	*	ns	***	ns	***	ns	ns	ns	ns	ns	**

Patient category: APAP, n = 21; IDILI, n = 39; HAV, n = 5; HBV, n = 5; HCV, n = 10.

Pearson’s correlation test was used to determine significance (ns, no significance; *P < 0.05; **P < 0.01; ***P < 0.0001).

Figure 1.  Biochemical parameters of liver failure patients. (A) Time from onset to hospitalization and serum levels of (B) AST and ALT, (C) bilirubin, and (D) alkaline phosphatase were compared between patients with acute liver failure of different etiologies. Statistical significance between IDILI patients (n = 39) and other patient groups (APAP, n = 21; Hepatitis A and B, n = 5 each) was determined by the t-test with Welch’s correction; levels of significance are indicated in the figure.

Figure 2.  T_H17-related cytokine/chemokine comparisons between patient groups. Serum concentrations of T_H17-related cytokines/chemokines (e.g., IL-17, IL-21, IL-6, and IL-1α) were measured by Luminex using a human multiplex kit. The statistical significance of any differences between the APAP (n = 21) and IDILI (n = 39) patients’ values were determined by the t-test with Welch’s correction; levels of significance are indicated in the figure. Data from patients in the Hepatitis A, B, and C virus groups are shown for comparison (n = 5, 5, and 10, respectively).

Figure 3.  Innate cytokine/chemokine comparisons between patient groups. Serum concentrations of innate cytokines/chemokines (e.g., MCP-1, IL-15, IP-10, and IFNγ) were measured by Luminex using a human multiplex kit. The statistical significance of any differences between the APAP (n = 21) and IDILI (n = 39) patients’ values were determined by the t-test with Welch’s correction; levels of significance are indicated in the figure. Data from patients in the Hepatitis A, B, and C virus groups are shown for comparison (n = 5, 5, and 10, respectively).

Figure 4.  Serum levels of BAFF. Serum concentrations of BAFF were measured by ELISA. The statistical significance of any difference between the APAP (n = 21) and IDILI (n = 39) patients’ values was determined by the t-test with Welch’s correction by the t-test with Welch’s correction; level of significance is indicated in the figure.

Figure 5.  Serum levels of ANA. Serum levels of ANA were measured using an ELISA kit that detects 9 different anti-nuclear antibodies. Serum samples were diluted in 1:100 and the manufacturer indicates that values greater than 10 should be considered positive. The statistical significance of any difference between the APAP (n = 21) and IDILI (n = 39) patients’ values was determined by the t-test with Welch’s correction; level of significance is indicated in the figure. Data from patients in the Hepatitis A, B, and C virus groups are shown for comparison (n = 5, 5, and 10, respectively).

Figure 6.  Serum levels of anti-MPO antibodies. Serum anti-MPO levels were determined (semi-quantitation) by an ELISA kit. Serum samples were diluted in 1:100. The statistical significance of any difference between the APAP (n = 21) and IDILI (n = 39) patients’ values was determined by the t-test with Welch’s correction; level of significance is indicated in the figure. Data from patients in the Hepatitis A, B, and C virus groups are shown for comparison (n = 5, 5, and 10, respectively).

Table 2.  Levels of IL-17, IL-21, IL-6, IP-10 (Luminex assay), ANA, and anti-MPO (ELISA assay) in individual IDILI patients.

Patient ID	Cause of liver failure	IL-21 (pg/mL)	IL-17 (pg/mL)	IL-6 (pg/mL)	ANA (U/mL)	Anti-MPO (EU/mL)	IP-10 (pg/mL)
12-015-04	ISONIAZID	191	<3.2	53	71	914	169
13-010-04	ISONIAZID	651	<3.2	9	<10	1263	294
13-088-01	ISONIAZID	453	<3.2	33	12	982	3549
13-133-02	ISONIAZID	211	<3.2	14	15	1684	96
14-005-02	ISONIAZID	1789	4.3	19	<10	1217	297
14-067-04	INH, PZA, RIFAMPIN	305	<3.2	60	<10	1214	276
12-020-01	PZA/RIFAMPIN	1864	<3.2	25	<10	1805	403
10-009-06	RIFAMPIN	1240	44.6	76	<10	1043	1162
13-015-02	NITROFURANTOIN	2122	<3.2	18	12	1190	130
13-067-04	NITROFURANTOIN	857	4.8	16	<10	1298	228
13-080-02	BACTRIM	1726	4.9	263	<10	930	1940
10-025-01	SULFADIAZINE	842	<3.2	1127	<10	1032	3419
11-021-04	TRIMETHOPRIM/SULFA	849	12.5	40	63	1166	407
15-002-02	BROMFENAC	1374	<3.2	99	<10	1339	95
13-003-03	TROGLITAZONE	128	4.2	13	<10	1145	188
13-047-01	PHENYTOIN	918	<3.2	197	<10	1016	>10000
14-037-02	PHENYTOIN	1742	5.5	664	11	1591	6369
13-129-02	PROPYLTHIOURACIL	1074	10.2	133	65	795	420
13-064-01	ALLOPURINOL	857	107.8	1042	<10	853	>10000
11-072-04	GEMTUZUMAB	781	3.3	1437	<10	1239	449
11-100-02	KAVA KAVA PHENYTOIN	854	3.3	154	<10	1611	73
13-016-01	PRAVASTATIN	1853	3.5	321	17	1568	455
14-007-04	CERIVASTATIN	4457	<3.2	59	<10	1365	573
15-039-03	ROSIGLITAZONE	1174	<3.2	615	<10	1216	294
13-145-04	DICLOFENAC	496	3.5	278	30	3113	>10000
10-061-01	CIPROFLOXACIN	250	5.8	24	<10	1272	868
11-153-02	ETODOLAC	906	8.2	32	25	1239	326
13-007-03	ZAFIRLUKAST	796	8.6	76	<10	1938	339
11-081-04	DISULFIRAM	790	22.6	70	<10	1101	532
10-027-06	QUETIAPINE	972	39.7	94	11	1347	488
14-042-04	HORNY GOAT WEED	2165	<3.2	228	15	1105	341
15-049-02	B6	729	3.3	64	<10	2273	92
16-007-06	ISOFLURANE	858	40.1	935	<10	1783	332
14-078-06	UNKNOWN DRUG	464	65.6	122	<10	2290	530
13-147-02	TAK-559	713	111.0	279	<10	1585	922
13-176-01	UNKNOWN DRUG	2408	<3.2	3.3	12	987	1829
13-039-02	THERMA SLIM	5623	<3.2	37	<10	1282	332
15-041-02	BLACK COHOSH	775	<3.2	37	<10	1577	304
13-004-02	HERBAL MEDS (MULTIPLE)	552	12.2	1140	13	1603	457