Table 1.

Immune Measures in sOP vs NOP Children

MUCOSAL (NP & MEF)
	sOP:NOP	Visit Type(s)	Ref
Innate Responses
Immune modulators-NP
MIP-1β	↓	AOM	30
CXCL5	↓	AOM	30
IL-8	↓, NSD	AOM	26,30
IL-6	↓	AOM, URI@Healthy	24,26,30
EGF	↓	AOM	30
EGFR	↓	AOM	30
Angiogenin	↓	AOM	30
ICAM-1	↓	AOM	30
IL-7	↓	AOM	31
IGFBP-4	↓	AOM	31
IL-23	↓	Healthy	24
TNFα, IL-6, IL-10, RANTES,	↓	URI@Healthy	26
MCP-1	NSD	AOM	26,30
IL-2	↑	AOM	26,31
			26
IL-2	NSD	URI@Healthy	26
IL-17a	NSD	AOM, URI@Healthy	26,31
IFN-γ	NSD	AOM, URI@Healthy	26,31
IL-1β, IL-8, MIP-1α	NSD	URI@Healthy	26
TLR2/4 (RNA)	↑	AOM	30
TLR2 (RNA) (Epithelials & Neutropils)	↑	AOM	30
ICAM-1	↓	AOM	30
Immune modulators-MEF
IL-2 (RNA)	↑	AOM	31
IL-8 (RNA)	↑	AOM	67
SLPI (RNA)	↑	AOM	67
MIP-1α (RNA)	↑	AOM	67
RANTES (RNA)	↓	AOM	67
IFNα1 (RNA)	↓	AOM	67
IRF7 (RNA)	↓	AOM	67
MAPK8 (RNA)	↓	AOM	67
TICAM2 (RNA)	↓	AOM	67
ZBP1 (RNA)	↓	AOM	67
Adaptive Responses
Antibodies
IgG to Spn & Mcat Ags	↓	Healthy	33,68
IgA to Spn & Mcat Ags	↓	Healthy	33,68
Colonization
Spn, NTHi, Mcat	↑	Healthy, URI@Healthy, AOM	26,33,68
Viral Infection
RSV	↑	AOM	48
URIs	↑	Healthy	26
BLOOD
	sOP:NOP	Visit Type(s)	Ref
Baseline Responses
PBMC (unstimulated)
IL-2	↓	AOM	31
IFN γ	↓	AOM	31
BAFF, APRIL	NSD	Healthy	42
APCs (unstimulated)
Total Monocytes & cDCs	↑	Healthy	25
MHC II	↓	Healthy & AOM	69
PBMC (R848 stimulated)
IL-1β, IL-6, IL-8, IL-10, IL-12, IFN-α, TNF-α, IFN-γ, CCL2, CCL4, CCL5, CXCL10	NSD	Healthy	25
APCs (R484 stimulated)
Intracellular IL-12, TNF-α, IFN-α	NSD	Healthy	25
Innate & Adaptive Responses
PBMC (HK-Spn stimulated)
IL-2, IL-4, IL-6, IL-10, IL-13	NSD	Healthy	24
IFN-γ	↓	Healthy	24
IL-17A	↓	Healthy	24
IL-21	↓	Healthy	24
IL-23	↓	Healthy	24
IL-2 (RNA)	↓	Healthy	24
IL-13 (RNA)	↓	Healthy	24
IL-17A (RNA)	↓	Healthy	24
IL-23 (RNA)	↓	Healthy	24
TGF-β (RNA)	↓	Healthy	24
IFN-γ (RNA)	↓	Healthy	24
TBX21 (RNA)	↓	Healthy	24
RORC (RNA)	↓	Healthy	24
FOXP3 (RNA)	↑	Healthy	24
Adaptive Responses
Antibodies
IgG to Spn, NTHi, Mcat Ags	↓	Healthy & AOM	34-36,40,43
Antibodies to pediatric vaccine Ags (DTaP, Hib, Polio, Spn PSs)	↓	Healthy	22,41,42
IgG to RSV	↓	Healthy	48
B cells
Total B cells	NSD	Healthy	41
BAFFR, TACI	↓	Healthy	42
BCMA	NSD	Healthy	42
BAFFR, TACI, B7-1, B7-2 (RNAs)	↓	Healthy	42
BCMA, CD40L (RNAs)	NSD	Healthy	42
%Memory B cells	↓	Healthy	41,42
%Memory B cells response to DTaP	↓	Healthy	40,41
%Switched memory	↓	Healthy	41
%Plasma cells	↓	Healthy	42
Spn Ag-specific ASCs	↓	Healthy	42
CD4+ T cells
Total CD4+ T-cells	NSD	Healthy	43
Naïve CD4+ T-cells	NSD	Healthy	43
Memory CD4+ T-cells	NSD	Healthy	43
CD4+ T-cells (HK-Spn stimulated)
pSTAT3	↓	Healthy	24
pSTAT3 (+Th17 cytokines)	NSD	Healthy	24
%CD4+ T-cells (HK-Spn stimulated)
IFN γ	NSD	Healthy	24
IL-2	↓	Healthy	24
IL-17A	↓	Healthy	24
TNF-α	↓	Healthy	24
%Naive CD4+ T-cells (HK-Spn stimulated)
IL-2	↓	Healthy	24
TNF-α	↓	Healthy	24
%Memory CD4+ T-cells (HK-Spn stimulated)
IFN γ	↓	Healthy	24
IL-2	↓	Healthy	24
IL-17A	↓	Healthy	24
TNF-α	↓	Healthy	24
%Memory CD4+ T-cells (Spn or NTHi antigen stimulated)
IFN γ	↓	Healthy	43
IL-2	↓	Healthy	43
IL-4	↓	Healthy	43
IL-17A	↓	Healthy	43
%Memory CD4+ T-cells (SEB stimulated)
IFN γ, IL-2, IL-4, IL-17a	NSD	Healthy	43

NSD: No statistical difference detected

AOM: Child with acute otitis media (AOM).

Healthy: Child at a normal healthy visit checkup.

URI@Healthy: Child came in during a normal healthy visit checkup but was diagnosed with an upper respiratory infection (URI).

NP: Nasopharyngeal

MEF: Middle ear fluid

PBMC: Peripheral blood mononuclear cells

Spn: S. pneumoniae; HK-Spn: heat killed Spn; NTHi: nontypeable H. influenzae; Mcat: Moraxella catarrhalis