T-Dependent Antigen Response (TDAR) Tests: Meta-Analysis of Results Generated Across Multiple Laboratories

Figures & data

TABLE 1 Results for control rats (Unstandardized)

Comparison	Strain	Immunoglobulin class^1	Number of rats	Mean ± S.D.	P
IV^2 KLH vs.	Sprague-Dawley	IgM	NKLH = 195	TiterKLH = 11 ± 2	0.02
IV SRBC			NSRBC = 16	TiterSRBC = 9 ± 1
IV KLH vs.	Sprague-Dawley	IgM	NIV = 26	TiterLog2 IV = 3 ± 2	0.0002
FP^3 KLH			NFP = 36	TiterLog2 FP = 4 ± 1
IV KLH vs.	Sprague-Dawley	IgG	NIV = 26	TiterLog2 IV = 3 ± 2	< 0.0001
FP KLH			NFP = 36	TiterLog2 FP = 5 ± 1
IV SRBC	Sprague-Dawley vs.	IgM	NSD = 15	PlaqueLog2 SD = 6 ± 1	< 0.0001
	Wistar-Han		NWH = 95	PlaqueLog2 WH = 7 ± 1
IV KLH	Sprague-Dawley vs.	IgM	NSD = 26	TiterLog2 SD = 3 ± 2	0.0006
	Wistar-Han		NWH = 20	TiterLog2 WH = 5 ± 1
IV KLH	Sprague-Dawley vs.	IgG	NSD = 26	TiterLog2 SD = 3 ± 2	0.00038
	Wistar-Han		NWH = 20	Titer Log2 WH = 1 ± 2

¹Antibody class (IgM or IgG) in response to either SRBC or KLH; ²IV = Intravenous; ³FP = Foot Pad.

TABLE 2 Results for control rats (Standardized)

Comparison	Strain	Immunoglobulin class^1	Number of rats	Mean score ± S.D.	P
IV^2 KLH vs.	Sprague-Dawley	IgM	NKLH = 221	KLH = −0.03 ± 0.95	0.0024
IV SRBC			NSRBC = 31	SRBC = −0.58 ± 0.91
IV KLH vs.	Sprague-Dawley	IgM	NIV = 221	IV = −0.03 ± 0.95	0.02
FP^3 KLH			NFP = 36	FP = 0.36 ± 0.57
IV SRBC	Sprague-Dawley vs.	IgM	NSD = 31	SD = −0.58 ± 0.91	< 0.0001
	Wistar-Han		NWH = 95	WH = 0.67 ± 0.74
IV KLH	Sprague-Dawley vs.	IgM	NSD = 221	SD = −0.03 ± 0.95	0.05
	Wistar-Han		NWH = 20	WH = 0.41 ± 0.30
IV KLH	Sprague-Dawley vs.	IgG	NSD = 78	SD = −0.14 ± 1.18	< 0.0001
	Wistar-Han		NWH = 20	WH = −1.33 ± 0.80

¹Antibody class (IgM or IgG) in response to either SRBC or KLH; ²IV = Intravenous; ³FP = Foot Pad.

FIG. 1 Effects of dexamethasone and cyclophosphamide on rat primary IgM response following intravenous injection of SRBC. Forest plots of standardized log-mean differences for anti-SRBC IgM responses: the area of the box represents how much each study contributes to the meta-analysis (% weight) and the center of the box shows the standardized mean drug effect size (i.e., in standard deviation units, with the underlying data on the log-scale) for each study. The overall effect size and the corresponding confidence interval are summarized at the bottom of the forest plot in a hollow diamond symbol.

FIG. 2 Effects of cyclophosphamide or cyclosporine on rat primary IgM response following intravenous injection of KLH. Forest plots of standardized log-mean differences for anti-KLH IgM responses: the area of the box represents how much each study contributes to the meta-analysis (% weight) and the center of the box shows the standardized mean drug effect size (i.e., in standard deviation units, with the underlying data on the log-scale) for each study. The overall effect size and the corresponding confidence interval are summarized at the bottom of the forest plot in a hollow diamond symbol.

TABLE 3 Results for drug effects

Antigen (route of immunization)	Drug	Immunoglobulin class	Number of studies	Test of heterogeneity among experiments Test of drug effect among experiments (Standardized mean difference)	Value of statistics	P
KLH (IV)	Cyclophosphamide	IgM	3	Heterogeneity Chi-Sq.	15.37	< 0.001
				Test of SMD = 0 (z-test)	3.21	0.001
KLH (IV)	Cyclophosphamide	IgG	3	Heterogeneity Chi-Sq.	0.33	0.57
				Test of SMD = 0 (z-test)	6.75	< 0.001
KLH (IV)	Cyclosporine	IgM	4	Heterogeneity Chi-Sq.	16.33	0.001
				Test of SMD = 0 (z-test)	4.96	< 0.001
KLH (IV)	Cyclosporine	IgG	2	Heterogeneity Chi-Sq.	22.79	< 0.001
				Test of SMD = 0 (z-test)	1.62	0.11
SRBC (IV)	Cyclophosphamide	IgM	8	Heterogeneity Chi-Sq.	60.49	< 0.001
				Test of SMD = 0 (z-test)	6.19	< 0.001
SRBC (IV)	Cyclophosphamide	IgG	6	Heterogeneity Chi-Sq.	58.35	< 0.001
				Test of SMD = 0 (z-test)	4.83	< 0.001
SRBC (IV)	Dexamethasone	IgM	2	Heterogeneity Chi-Sq.	0.04	0.85
				Test of SMD = 0 (z-test)	3.83	< 0.001

TABLE 4 Results for effect of cyclophosphamide across antigens (random effects regression model)

Antigen	Immunoglobulin class	Number of Studies	Pooled Standardized mean difference	95% CI^1		Effect of cycophosphamide on KLH vs. SRBC
KLH	IgM	3	3.95	1.54	6.36
SRBC	IgM	2	5.17	3.59	6.75	P < 0.05

¹95% Confidence Intervals