Figure 1. Flow of Information Through the Stages of the Meta-Analysis, Including Reasons

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SupplementalInformation

Figure 1. Flow of information through the stages of the meta-analysis, including reasons for excluding full text articles.

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Table S1. Study characteristics
Study / Cytokine / ASD n / Controls n / ASD % Male / Control % Male / ASD Age Mean (SD) unless noted / Control Age Mean (SD) unless noted / Fraction
Al-Ayadhi 2005 (1) / IL-1, IL-6, TNF-α / 77 / 77 / 92 / 92 / 8.8 (0.5) / Matched / serum
Ashwood et al. 2008 (2) / TGF-β1 / 75 / 36 / 91 / 67 / 3.4 (3.0-4.2) Median (IQR) / 3.6 (2.8-4.5) Median (IQR) / plasma
Ashwood et al. 2011a (3) / Eotaxin, MCP-1, RANTES / 80 / 58 / 84 / 67 / 3.6(3.0-4.5) Median (IQR) / 3.6 (2.8-4.3) Median (IQR) / plasma
Ashwood et al. 2011b (4) / IL-1β, IL-6, IL-8, IL-12(p40) / 97 / 87 / 87 / 82 / 3.4(2.9-4.3) Median (IQR) / 3.4 (2.8-4.1) Median (IQR) / plasma
Croonenberghs et al. 2002 (5) / IL-1RA, IL-6 / 13 / 13 / 100 / 100 / 14.5(1.8) 12-18 / 15.1(1.5) / serum
Wakkad & Saleh 2006 (6) / IL-1β, IL-6 / 21 / 21 / 76 / 62 / 7.0 (1.7) / 7.8 (2.7) / serum
El-Ansary & Al-Ayadhi 2012 (7) / IFN-γ / 20 / 19 / 100 / 100 / 3 - 16 (Range) / 3 - 16 (Range) / plasma
Enstom et al. 2008 (8) / IL-23 / 40 / 20 / 90 / 80 / 3.4 (2.1-4.8) Median (IQR) / 3.7 (2.6-5.2) Median (IQR) / plasma
Hashim et al. 2013 (9) / IL-17, IL-23, TGF-β1 / 50 / 50 / 54 / 60 / 8.7(1.2) / 9.1(1.7) / plasma
Manzardo et al. 2012 (10) / G-CSF, IL-1α, IL-6, MIP-1α, MIP-1β / 99 / 40 / 75 / 70 / Male 7.82(1.5) Female 7.72(1.8) / Male 7.94(1.7) Female 7.25(1.8) / plasma
Napolioni et al. 2013 (11) / Eotaxin, G-CSF, IFN-γ, IL-10,IL-12(p40), IL-17, IL-1RA, IL-1α, IL-1β, IL-4, IL-6, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, TNF-α / 25 / 25 / 100 / 100 / 8.1 (3.7) / 7.4 (3.1) / plasma
Okada et al. 2007 (12) / TGF-β1 / 19 / 21 / 100 / 100 / 22.7 (2.3) / 23.4 (2.6) / serum
Ricci et al. 2013 (13) / IL-1β, IL-6, IL-23, TNF-α / 29 / 29 / 93 / 93 / 2-21 (Range) / 2-21 (Range) / serum
Singh 1996 (14) / IFN-γ / 20 / 20 / 80 / 65 / 10.7 / 10.4 / plasma
Suzuki et al. 2011 (15) / Eotaxin, G-CSF, IFN-γ, IL-10, IL12(p40), IL-17, IL-1RA, IL-1α, IL-1β, IL-4, IL-6, IL-8, MCP-1, MIP-1α, MIP-1β, RANTES, TNF-α / 28 / 28 / 100 / 100 / 12.1(3.3) / 12.3(2.3) / plasma
Sweeten et al. 2004 (16) / IFN-γ, IL-1β, TNF-α / 29 / 27 / 86 / 85 / 6.1(2.8) / 6.5(2.5) / plasma
Tostes et al. 2012 (17) / IFN-γ, IL-1β, IL-2, IL-4, IL-6, IL-10, TNF-α / 24 / 24 / 75 / 75 / 7.4 (2.7) / 7.2(1.8) / plasma
G-CSF, granulocyte colony-stimulating factor; IFN-γ, interferon-γ; IL, interleukin; IL-1RA, IL-1 receptor antagonist; MCP-1, monocyte chemotactic protein-1; MIP-1α, macrophage inflammatory protein-1α; RANTES, regulated on activation, normal t cell expressed and secreted; TGF-β1, transforming growth factor-β1; TNF-α, tumor necrosis factor-α

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Table S2. Cytokine selection procedure
Number of cytokines analysed in study / IL6 / TNFα / IFNγ / IL1β / IL17 / Eotaxin / IL10 / IL12p40 / IL4 / IL8 / MCP1 / MIP1α / MIP1β / IL2 / IL13 / G-CSF / IL1RA / IL1α / IL23
Suzuki et al. 2011 (15) / 42 / + / + / + / + / + / + / + / + / + / + / + / + / + / + / + / + / +
Napolioni et al. 2013 (11) / 39 / + / + / + / + / + / + / + / + / + / + / + / + / + / + / + / + / + / +
Manzardo et al. 2012 (10) / 29 / + / +a / +a / +a / +a / +a / +a / +a / +a / + / + / +a / + / +
Ashwood et al. 2011b (4) / 12 / + / +a / +a / + / +a / + / +a / + / +a / +a
Tostes et al. 2012 (17) / 7 / + / + / + / + / + / + / +
Ashwood et al. 2011a (3) / 6 / + / + / +a / +a
Singh 1996 (14) / 6 / +a / +a / +
Ricci et al. 2013 (13) / 6 / + / + / + / +a / +
Sweeten et al. 2004 (16) / 3 / + / + / +
Hashim et al. 2013 (9) / 3 / + / +
Al-Ayadhi 2005 (1) / 3 / + / +
Croonenberghs et al. 2002 (5) / 3 / + / +
Singh et al. 1991 (18) d / 3
El-Ansary & Al-Ayadhi 2012 (7) / 2 / +
Enstome et al. 2008 (8) / 2 / +a / +
Wakkad & Saleh 2006 (6) / 2 / + / +
El-Ansary et al. 2011 (19) d / 2 / +c / +c
Jyonouchi et al. 2001 (20) d / 2
Ashwood et al. 2008 (2) / 1
Okada et al. 2007 (12) / 1
AL-Ayadhi & Mostafa 2011 (21) d / 1
AL-Ayadhi & Mostafa 2012 (22) d / 1
Grigorenko et al. 2008 (23) d / 1
Studies reporting cytokine / 11 / 10 / 8 / 8 / 5 / 4 / 4 / 4 / 4 / 4 / 4 / 4 / 4 / 4 / 4 / 3 / 3 / 3 / 3
Studies included in meta-analysis / 9 / 6 / 6 / 7 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 3 / 0 / 0 / 3 / 3 / 3 / 3
+ Plasma or sera concentration of cytokine reported in study. aNo p-value reported; bPlasma or sera concentration of cytokine available in less than 3 studies; cMethods used to measure cytokine concentrations not reported; dNo cytokines in study met selection criteria
Table S2. Continued
RANTES / TGFβ1 / IL5 / IL12p70 / GMCSF / IP10 / IL12 / IL16 / IL7 / MCP3 / MCSF / MIG / TNFβ / IFNα2 / IL2Rα / IL9 / MIF / sTNFRI / sTNFRII
Suzuki et al. 2011 (15) / + / + / + / +b / + / + / + / + / + / + / +b / +b / +b / +b
Napolioni et al. 2013 (11) / + / + / + / +b / + / + / + / + / + / +b / +b
Manzardo et al. 2012 (10) / +a / +a / +a / + / +a / +a / +a
Ashwood et al. 2011b (4) / +a / +a
Tostes et al. 2012 (17)
Ashwood et al. 2011a (3) / + / +a
Singh 1996 (14) / +
Ricci et al. 2013 (13) / +
Sweeten et al. 2004 (16)
Hashim et al. 2013 (9) / +
Al-Ayadhi 2005 (1)
Croonenberghs et al. 2002 (5)
Singh et al. 1991 (18) d
El-Ansary & Al-Ayadhi 2012 (7)
Enstome et al. 2008 (8)
Wakkad & Saleh 2006 (6)
El-Ansary et al. 2011 (19) d
Jyonouchi et al. 2001 (20) d / +b / +b
Ashwood et al. 2008 (2) / +
Okada et al. 2007 (12) / +
AL-Ayadhi & Mostafa 2011 (21) d
AL-Ayadhi & Mostafa 2012 (22) d
Grigorenko et al. 2008 (23) d / +b
Studies reporting cytokine / 3 / 3 / 3 / 3 / 3 / 3 / 2 / 2 / 2 / 2 / 2 / 2 / 2 / 2 / 2 / 2 / 2 / 2 / 2
Studies included in meta-analysis / 3 / 3 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0
+ Plasma or sera concentration of cytokine reported in study. aNo p-value reported; bPlasma or sera concentration of cytokine available in less than 3 studies; cMethods used to measure cytokine concentrations not reported; dNo cytokines in study met selection criteria
Table S2. Continued
VEGF / BLC / CTACK / EGF / Eotaxin2 / FGF2 / Frantalkine / GRO / GROα / HGF / I-309 / ICAM-1 / IFNα / IL1 / IL11 / IL15 / IL17A / IL18
Suzuki et al. 2011 (15) / +b / +b / +b / +b / +b
Napolioni et al. 2013 (11) / +b / +b / +b / +b / +b / +b
Manzardo et al. 2012 (10) / +a / +b / +a / +b / +a
Ashwood et al. 2011b (4)
Tostes et al. 2012 (17)
Ashwood et al. 2011a (3)
Singh 1996 (14) / +a
Ricci et al. 2013 (13)
Sweeten et al. 2004 (16)
Hashim et al. 2013 (9)
Al-Ayadhi 2005 (1) / +b
Croonenberghs et al. 2002 (5)
Singh et al. 1991 (18) d
El-Ansary & Al-Ayadhi 2012 (7)
Enstome et al. 2008 (8)
Wakkad & Saleh 2006 (6)
El-Ansary et al. 2011 (19) d
Jyonouchi et al. 2001 (20) d
Ashwood et al. 2008 (2)
Okada et al. 2007 (12)
AL-Ayadhi & Mostafa 2011 (21) d
AL-Ayadhi & Mostafa 2012 (22) d / +b
Grigorenko et al. 2008 (23) d
Studies reporting cytokine / 2 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1
Studies included in meta-analysis / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0
+ Plasma or sera concentration of cytokine reported in study. aNo p-value reported; bPlasma or sera concentration of cytokine available in less than 3 studies; cMethods used to measure cytokine concentrations not reported; dNo cytokines in study met selection criteria
Table S2. Continued
IL3 / IL6sR / MDC / MIP1δ / Osteopontin / SCF / SCGFβ / SDF1α / sICAM1 / sIL1 / sIL2 / sIL2R / TGFα / TGFβ / TIMP1 / TIMP2 / TRAIL / βNGF
Suzuki et al. 2011 (15) / +b / +b / +b / +b / +b / +b
Napolioni et al. 2013 (11) / +b / +b / +b / +b
Manzardo et al. 2012 (10) / +a / +b
Ashwood et al. 2011b (4)
Tostes et al. 2012 (17)
Ashwood et al. 2011a (3)
Singh 1996 (14) / +b
Ricci et al. 2013 (13)
Sweeten et al. 2004 (16)
Hashim et al. 2013 (9)
Al-Ayadhi 2005 (1)
Croonenberghs et al. 2002 (5)
Singh et al. 1991 (18) d / +b / +b / +b
El-Ansary & Al-Ayadhi 2012 (7) / +b
Enstome et al. 2008 (8)
Wakkad & Saleh 2006 (6)
El-Ansary et al. 2011 (19) d
Jyonouchi et al. 2001 (20) d
Ashwood et al. 2008 (2)
Okada et al. 2007 (12)
AL-Ayadhi & Mostafa 2011 (21) d / +b
AL-Ayadhi & Mostafa 2012 (22) d
Grigorenko et al. 2008 (23) d
Studies reporting cytokine / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1 / 1
Studies included in meta-analysis / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0 / 0
+ Plasma or sera concentration of cytokine reported in study. aNo p-value reported; bPlasma or sera concentration of cytokine available in less than 3 studies; cMethods used to measure cytokine concentrations not reported; dNo cytokines in study met selection criteria
BLC, B lymphocyte chemoattractant; CTACK, cutaneous T cell-attracting chemokine; EGF, epidermal growth factor; FGF2, fibroblast growth factor 2; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte macrophage colony-stimulating factor; GRO, growth regulated protein; GRO-α, growth regulated protein-α ; HGF, hepatocyte growth factor; ICAM-1, intercellular adhesion molecule-1; sICAM-1, soluble ICAM-1; IFN- α, interferon- α; IFN-γ, interferon-γ; IL, interleukin; IL-1Rα, IL-1 receptor α; IL-1RA, IL-1 receptor antagonist; IL-6sR, IL-6 soluble receptor; IP-10, interferon gamma-inducible protein 10; MCP-1, monocyte chemotactic protein-1; MDC, macrophage derived chemokine; MIF, migration inhibitory factor; MIG, monokine induced by gamma interferon; MIP-1α, macrophage inflammatory protein-1α; β-NGF, β-nerve growth factor; RANTES, regulated on activation, normal t cell expressed and secreted; SCF, stem cell factor; SCGF-β, stem cell growth factor-β; SDF-1α, stromal cell-derived factor-1α; TGF-β1, transforming growth factor-β1; TIMP-1 , tissue inhibitor of metalloproteinase-1; TNF-α, tumor necrosis factor-α; TRAIL, TNF-related apoptosis-inducing ligand; VEGF, vascular endothelial growth factor.

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