antibody and b cell responses may control circulating lipopolysaccharide in patients with hiv...

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Antibody and B cell responses may control circulating lipopolysaccharide in patients with HIV infection Lim A 1 , Amini A 1 , D’Orsogna L 2 , Rajasuriar R 3 , Lewin S 3,4 , Purcell D 5 , Price P 1 , French MA 1,2 1. School of Pathology and Laboratory Medicine, University of Western Australia 2. Department of Clinical Immunology, Royal Perth Hospital, Perth 3. Alfred Hospital, Melbourne 4. Monash University, Melbourne 5. Department of Microbiology and Immunology, University of Melbourne

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Page 1: Antibody and B cell responses may control circulating lipopolysaccharide in patients with HIV infection Lim A 1, Amini A 1, D’Orsogna L 2, Rajasuriar R

Antibody and B cell responses may control circulating lipopolysaccharide in

patients with HIV infection

Lim A1, Amini A1, D’Orsogna L2, Rajasuriar R3, Lewin S3,4, Purcell D5, Price P1, French MA1,2

1. School of Pathology and Laboratory Medicine, University of Western Australia 2. Department of Clinical Immunology, Royal Perth Hospital, Perth 3. Alfred Hospital, Melbourne 4. Monash University, Melbourne 5. Department of Microbiology and Immunology, University of Melbourne

Page 2: Antibody and B cell responses may control circulating lipopolysaccharide in patients with HIV infection Lim A 1, Amini A 1, D’Orsogna L 2, Rajasuriar R

Marginal zone (IgM+

memory) B cells and IgA antibodies respond to gut microbial products

Cerutti A, Rescigno M. Immunity 2008; 28:740-50

Kraal G. Nature Immunol 2008; 9:11-12

Page 3: Antibody and B cell responses may control circulating lipopolysaccharide in patients with HIV infection Lim A 1, Amini A 1, D’Orsogna L 2, Rajasuriar R

Plasma levels of LPS are inversely correlated with serum levels of antibodies to LPS in

ART-naïve HIV patients

Page 4: Antibody and B cell responses may control circulating lipopolysaccharide in patients with HIV infection Lim A 1, Amini A 1, D’Orsogna L 2, Rajasuriar R

LPS-specific IgG antibodies correlate with IgM+

memory B cell counts in ART-naïve patients

Page 5: Antibody and B cell responses may control circulating lipopolysaccharide in patients with HIV infection Lim A 1, Amini A 1, D’Orsogna L 2, Rajasuriar R

Better immune reconstitution on ART is associated with lower plasma LPS and serum

anti-LPS

Page 6: Antibody and B cell responses may control circulating lipopolysaccharide in patients with HIV infection Lim A 1, Amini A 1, D’Orsogna L 2, Rajasuriar R

Summary• In ART-naïve patients:• Serum levels of IgG and IgA antibodies to LPS are

negatively correlated with plasma LPS levels• Serum levels of IgG anti-LPS are positively correlated

with circulating IgM+ memory B cell counts• Serum IgA levels are strongly correlated with serum

levels of IgA antibodies to LPS

• In ART-treated patients:• Better immune reconstitution (higher CD4+ T cell

and switched memory B cell counts) is associated with lower levels of LPS and antibodies to LPS

Page 7: Antibody and B cell responses may control circulating lipopolysaccharide in patients with HIV infection Lim A 1, Amini A 1, D’Orsogna L 2, Rajasuriar R

Conclusions• Plasma LPS levels in ART-naive HIV patients

may be determined by immune responses against LPS, as well as by increased gut permeability

• High serum IgA levels in untreated HIV infection may reflect an IgA antibody response against LPS