Complement Deficiencies

Colten, Harvey R.; Rosen, Fred S.

doi:10.1146/annurev.iy.10.040192.004113

Cited by 122 publications

(64 citation statements)

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“…This is where the target MUC1 peptide and carbohydrates begin. If complement activation occurs at sites more distant than 100 Å from the cell membrane, the MAC would not form or if formed would not reach the cell membrane and a number of serum proteins would quickly inactivate the forming MAC (47). Complement-inactivating factors cannot explain these findings because CDC was readily induced by Abs against glycolipids in the same experiments and same two cell lines that could not be lysed by mucin Abs.…”

Section: Discussionmentioning

confidence: 96%

Antibodies against Tumor Cell Glycolipids and Proteins, but Not Mucins, Mediate Complement-Dependent Cytotoxicity

Ragupathi¹,

Liu²,

Musselli³

et al. 2005

The Journal of Immunology

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One of several effector mechanisms thought to contribute to Ab efficacy against cancer is complement-dependent cytotoxicity (CDC). Serological analysis of a series of clinical trials conducted over a 10-year period suggested that six vaccines containing different glycolipids induced Abs mediating CDC whereas four vaccines containing carbohydrate or peptide epitopes carried almost exclusively by mucin molecules induced Abs that did not mediate CDC. To explore this further, we have now compared cell surface reactivity using flow cytometry assays (FACS), complement-fixing ability, and CDC activity of a panel of mAbs and immune sera from these trials on the same two tumor cell lines. Abs against glycolipids GM2, globo H and Lewis Y, protein KSA (epithelial cell adhesion molecule, also known as EpCAM) and mucin Ags Tn, sialylated Tn, Thomsen Friedenreich (TF), and MUC1 all reacted comparably by FACS with tumor cells expressing these Ags. Compared with the strong complement binding and CDC with Abs against glycolipids and KSA, complement binding was diminished with Abs against mucin Ags and no CDC was detected. A major difference between these two groups of Ags is proximity to the cell membrane. Glycolipids and globular glycoproteins extend less than 100 Å from the cell membrane while mucins extend up to 5000 Å. Although complement activation at sites remote from the cell membrane has long been known as a mechanism for resistance from complement lysis in bacteria, it is identified here for the first time as a factor which may contribute to resistance from CDC against cancer cells.

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Section: Discussionmentioning

confidence: 96%

Antibodies against Tumor Cell Glycolipids and Proteins, but Not Mucins, Mediate Complement-Dependent Cytotoxicity

Ragupathi¹,

Liu²,

Musselli³

et al. 2005

The Journal of Immunology

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“…Significantly more mixed infections of B. garinii-B. valaisiana composition than expected under neutralist assumptions were observed in the data set from Slovakia (Slovakia, 2 2 ϭ 96.1, P ϭ 1.05 ϫ 10 Ϫ20 ; Latvia, 1 2 ϭ 6.41, P ϭ 0.0113; and Germany, 1 2 ϭ 1.38, P ϭ 0.240). The present study yielded two major findings: (i) the majority of infected ticks harbored one genospecies only, and (ii) B. garinii and B. valaisiana constituted the majority of multiple infections, whereas the combination of B. garinii and B. afzelii occurred significantly less frequently than expected.…”

mentioning

confidence: 77%

Distinct Combinations of Borrelia burgdorferi Sensu Lato Genospecies Found in Individual Questing Ticks from Europe

Kurtenbach

Michelis

Sewell

et al. 2001

Appl Environ Microbiol

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The genetic diversity of Borrelia burgdorferi sensu lato was assessed in individual adult Ixodes ricinus ticks from Europe by direct PCR amplification of spirochetal DNA followed by genospecies-specific hybridization. Analysis of mixed infections in the ticks showed that B. garinii and B. valaisiana segregate from B. afzelii. This and previous findings suggest that host complement interacts with spirochetes in the tick, thereby playing an important role in the ecology of Lyme borreliosis.

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“…In bacterial infections, complement-induced inflammatory mechanisms may be more important than lytic mechanisms, because consequences of hereditary deficiency states involving either the classical or alternate complement pathways are severe, whereas deficiencies of the membrane attack complex are comparatively less important (22).…”

Section: Discussionmentioning

confidence: 99%

Vaccination of Small Cell Lung Cancer Patients with Polysialic Acid orN-Propionylated Polysialic Acid Conjugated to Keyhole Limpet Hemocyanin

Krug¹,

Ragupathi

Ng³

et al. 2004

Clinical Cancer Research

107

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Purpose: Long chain polysialic acid (polySA) is a side chain on embryonal neural cell adhesion molecules that, in the adult, is largely restricted to small cell lung cancer (SCLC). Long chains of polySA are also expressed on group B meningococcus. In this clinical trial, we aimed to elicit an immune response against polysialic acid to target clinically inapparent residual disease in patients with SCLC who had successfully completed initial therapy.Experimental Conclusions: Vaccination with NP-polySA-KLH, but not polySA-KLH, resulted in a consistent high titer antibody response. We are now conducting a de-escalation dosing study with NP-polySA-KLH to better assess the immunogenicity, toxicities, and optimal dose of this vaccine. We plan to incorporate this vaccine as a component of a polyvalent vaccine with GM2, fucosylated GM1, and Globo H to target SCLC.

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Complement Deficiencies

Cited by 122 publications

References 0 publications

Antibodies against Tumor Cell Glycolipids and Proteins, but Not Mucins, Mediate Complement-Dependent Cytotoxicity

Antibodies against Tumor Cell Glycolipids and Proteins, but Not Mucins, Mediate Complement-Dependent Cytotoxicity

Distinct Combinations of Borrelia burgdorferi Sensu Lato Genospecies Found in Individual Questing Ticks from Europe

Vaccination of Small Cell Lung Cancer Patients with Polysialic Acid orN-Propionylated Polysialic Acid Conjugated to Keyhole Limpet Hemocyanin

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