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In Vitro Assay to Evaluate the Impact of Immunoregulatory Pathways on HIV-specific CD4 T Cell Effector Function
Published on: October 15, 2013
Immunological analysis in paediatric HIV patients at different stages of the disease
Y C Lian1, M Della-Negra, R Rutz
1Institute of Infectology Emílio Ribas, São Paulo, Brazil.
Insights
Complement activation occurs in all pediatric HIV stages, correlating with disease severity and immune status. Mannan-binding lectin (MBL) did not emerge as a risk factor in this study.
Area of Science:
- Immunology
- Virology
- Pediatrics
Background:
- Limited clinical data exists on complement system function in well-characterized pediatric HIV patients.
- Understanding humoral immunity, including complement and immunoglobulins, is crucial for managing pediatric HIV.
Purpose of the Study:
- To evaluate the complement system and immunoglobulin levels in HIV-infected children.
- To correlate these immune markers with the clinical and immunological staging of pediatric HIV disease.
Main Methods:
- Analysis of 127 HIV-infected children (11-134 months) based on CDC clinical and immunological criteria (CD4+ T cell count).
- Assessed complement pathways (CH50, APH50), mannan-binding lectin (MBL), C4 variants, and C3 split product C3d.
- Measured CD4+, CD8+ lymphocyte counts and immunoglobulin concentrations.
Main Results:
- Complement activation and consumption were observed in all patients, correlating with disease activity.
- Activated classical and alternative pathways and elevated C3d significantly correlated with advanced immunologic categories (3 and 1).
- Low MBL levels were found in 13/127 patients without disease severity correlation; C4B deficiency was noted in three patients.
Conclusions:
- A strong, ongoing complement activation is present across all stages of pediatric HIV infection.
- Complement activation markers are significantly associated with disease severity and immune decline in children with HIV.
- Mannan-binding lectin (MBL) was not identified as a risk factor for HIV progression in this cohort.
Abstract:
There are only few clinical studies on complement in well-defined (or characterized) paediatric HIV patients. Aim of this study was to evaluate the complement system and immunoglobulins in HIV-infected children and to correlate data to stage of disease. Blood samples of 127 HIV-infected children (11-134 months; 62 male : 65 female) were collected in order to evaluate humoral immunity. The patients were classified according to CDC clinical (N-asymptomatic; A-mild symptoms such as common recurrent infections; B-moderate symptoms such as Candidiasis and herpes infections, meningitis, sepsis and anaemia; C-severe symptoms such as opportunistic infections and neoplasia) and with respect to immunological criteria (T CD4(+) cell count). Analysis of complement system included the classical (CH50), alternative (APH50) pathway activities and plasma concentrations of mannan-binding lectin (MBL), of the C4 allotypic variants C4A and C4B. (ELISA), and of the C3 split product C3d (rocket immunoeletrophoresis). Immunodiagnosis also included CD4(+) and CD8(+) lymphocyte count and immunoglobulin concentrations. Complement activation and consumption was observed in all patients correlating with disease activity. Activated classical and alternative pathways and elevated C3d were significantly correlated with immunologic category 3. C3d levels were also significantly correlated with immunologic category 1. Undetectable CH50 and APH50 were found in two (group C) and 10 patients (n = 2, A = 2, B = 2, C = 4), respectively. Low MBL values were found in 13/127 but without correlation to disease severity. Undetectable C4B levels were observed in three patients, favouring the diagnosis of a complete deficiency. Although not related to clinical symptomatology, a strong ongoing complement activation can be observed in all stages of HIV infection. In contrast to earlier reports MBL could not be considered as a risk factor for HIV.

