Table I.

Summary of the germ-free phenotypes of spontaneous or inducible models of lupus-like disease.^a

References	Strain/Model	Autoimmune Serologies	Spleen	Kidneys	Other Manifestations/Findings
East et at29
	NZB GF	Coombs+ at 8-11mo. ANA+ (6 mo.): 25%	8 - 11 mo.: Enlarged, thin, tough, dark purple	Histology N/A	Ceca: enlarged, distended Superficial LNs: small, difficult to detect Virus-like particles: at 6, 8, 11 mo. Antibodies to polyoma virus: not detected
	NZB Conv	Coombs+ at 4-6 mo. ANA+ (>6 mo.): 20-30%	8 - 11 mo.: Enlarged, thick, spongy, pink-red	Histology N/A	Ceca: not detailed Superficial LNs: prominent, palpable Virus-like particles: at 1week-14 mo. Antibodies to polyoma virus: detectable
Barnes & Tuffrey27
	NZB GF	Coombs+: N/A ANA+ (>5 mo.) 50%	Not Studied	Not Studied	Thymus (post-mortem): similar to Conv NZB
	NZB Conv	Coombs+ at 4 mo. ANA+ (5-6 mo.): 22%	Not Studied	Not Studied	Thymus (post mortem): germinal follicle formation and accumulation of plasma cells
East & Branca28
	NZB GF	Coombs+ unequivocal at 10-17 mo.	Splenomegaly (later onset): average wt 0.51g(0.1-0.7g); smaller germinal centers at 8 mo.	Glomerulonephritis present (at 8 mo.: enlarged glomeruli, mesangial proliferation)	Thymus (6-10 mo.): larger than Conv Inguinal LN (8 mo.): involuted Mesenteric LN (8 mo.): smaller, lymphocyte depleted Anemia: less severe at 9-10 mo. (hematocrit 32-40%)
	NZB Conv	Coombs+ “earlier” than GF	Splenomegaly; average wt 1.26g (0.4-2.3g)	Glomerulonephritis present (severity not detailed)	Thymus (6-10 mo.): smaller than GF (not detailed) Inguinal LN (8 mo.): large, active follicles Mesenteric LN (8 mo.): larger (not detailed) Anemia: severe at 9-10 mo. (hematocrit 17-38%)
Unni et at32
	NZB GF	Coombs+ “no significant difference” to Conv (but lower incidence at 6 mo. with 0-20% depending on sex) ANA+ at 6 mo. (also higher than Conv at 9 and 12 mo.; p<0.025)	N/A	Decreased incidence and severity of glomerular lesions and lymphocytic infiltrates than Conv (at 12 mo.; p<0.005)	Ceca: dilated at 6-12 mo. Liver (12 mo.): lower incidence of periportal infiltrate (8 of 27 mice) Lung (12 mo.): lower incidence of lymphocytic infiltrates (8 of 27 mice) γ-globulins lower than Conv in all age groups (p<0.01)
	NZB Conv	Coombs+ at 6 mo. 40- 60% ANA+ at 12 mo.	N/A	Progressive glomerular lesions and lymphocytic infiltrates (greater than GF at 12 mo.); greater proteinuria	Ceca: not detailed Liver (12 mo.): frequent periportal infiltrates (31 of 39 mice) Lungs (12 mo.): frequent lymphocytic infiltrates (32 of 39 mice) γ-globulins higher than GF at 3, 6, 9, 12 mo.
Maldonado et al30
	MRL/MpJ- Faslpr GF	Trend towards higher IgG2a and anti-Sm at 5 mo. Anti-dsDNA+: 89%	No difference in wt at 5 mo.	Similar glomerulonephritis and proteinuria at 5 mo. (with antigen-free diet: little glomerular disease, little vascular/interstitial changes, minimal C3 deposits, little proteinuria)	Ceca: enlarged (but mitigated if fed with antigen-free diet) Ear lesions: absent (but present in 7 of 8 females and 1 of 9 males fed with antigen-free diet) LN: No difference in LN T cell subsets and extensive lymphadenopathy (LN weight from male mice fed with antigen-free diet was lower than that of GF mice fed with natural ingredients)
	MRL/MpJ- Faslpr Conv	Higher IgM (p=0.05) and anti-ssDNA (p=0.04) at 5 mo. Anti-dsDNA+: 43%	Same spleen wt at 5 mo. as GF	Similar glomerulonephritis and proteinuria at 5 mo. as GF	Ceca: normal size (not detailed) Ear lesions: “typical for MRL-lpr” (not detailed) LN: extensive lymphadenopathy; same LN T cell subsets as in GF
Mizutani et al31
	BALB/c GF treated with i.p. pristane	Anti-RNP/Smith IgG at 6 mo. post-treatment lower than Conv (p<0.000l)	Germinal center formation “at low frequency” lymphoid follicles poorly developed	Histology: N/A	Ceca: enlarged (in all 62 mice) Pristane-induced IL-6, IL-12, hyper-γ-globulinemia detectable (no comparison made to Conv)
	BALB/c Conv treated with i.p. pristane	Anti-RNP/Smith IgG at 6 mo. higher than GF (but similar levels of anti-Su)	Formation of germinal centers and lymphoid follicles (not detailed)	Histology: N/A	Ceca: normal size (not detailed) Pristane-induced IL-6, IL-12, hyper-γ-globulinemia not detailed

^aComparison of published germ-free (GF) versus conventionally raised (Conv) mice that develop spontaneous or inducible features of systemic, lupus-like autoimmunity. Cecal size (if reported) is listed under “Other Manifestations/Findings” as an indirect measure of a successful GF state. Abbreviations: GF, germ-free; Conv, conventional; ANA, antinuclear antibodies; N/A, not assessed; mo., months; LN, lymph nodes; wt, weight; i.p., intraperitoneal.