Antiphospholipid antibodies in children

I'm going to break the ice here and make the first student post because class this week got me all excited! Just this past week the lab I work in submitted an abstract about antiphospholipid antibody syndrome (APS) in children. In short, this syndrome is characterized by blood clots associated with so-called “antiphospholipid antibodies” (although, these antibodies generally don’t bind phospholipid, but rather phospholipid-binding proteins…for an excellent, in depth review see:
http://www.ncbi.nlm.nih.gov/pubmed/12871358?ordinalpos=27&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum ).

To be diagnosed with APS a person must present with a thrombosis (blood clot). They then need to have positive tests for antiphospholipid antibodies on two separate occasions that are at least three months apart. So, by definition, the people with APS consistently have these antiphospholipid antibodies, which are not usually present in normal, healthy people.

These so-called “antiphospholipid antibodies” are not necessarily directed against phospholipids - that is just the term that has been given to the population of antibodies that seem to be common in people with APS. For our discussion, it isn’t essential to understand what the antibodies are directed against because how each antibody may activate blood clotting isn’t entirely understood. For our purposes, all that needs to be understood is that these patients have abnormally high levels of autoantibody for long periods of time. This is true even when these APS patients are compared to other children who have had blood clots.

Our study focused on children who were diagnosed with APS. APS is a rather complex syndrome that is fairly common in adults with thrombosis but has been little studied in children. Our lab (which includes fellow classmates ChrisB7630 and MeghanC7630) started studying APS in children in hopes of finding a relationship between certain antiphospholipid antibodies and thrombotic outcome, with the long-term goal of using this data to improve clinical care for children affected with APS. Our findings (as presented in our abstract which follows in a comment - beware, it is quite technical!) found that, in general, children who have persistently positive (positive for at least three months) IgM antibodies are more likely to have had recurrent blood clots. After class we started to wonder if maybe the high levels of IgM themselves are responsible for recurrence, as high concentrations the big IgM molecules could make the blood "sticky". Or maybe having consistently high IgM levels is indicative of some sort of underlying inflammation that may have a role in thrombosis.

I’m very much looking forward to this class! I’m excited to see what light others can shine on our work. Yay!

Do bugs control your immune response?

We are multicellular creatures (metazoans) with about 30 million million cells. Each cell lives in its own tiny microenvironment which is slightly different from all others; no two cells are identical in position, function, or future. All cells depend for survival on interactions with their neighbors, mediated either by direct contacts or through soluble molecules like chemokines and cytokines, growth and survival factors. This makes me think that all instances of damage or infection that stimulate the innate immune system will be different, too. If it’s an RNA virus, for example, or an E. coli, the array of Pattern-Recognition Receptors that are stimulated will be different, and the soup of chemokines and cytokines made by affected cells will therefore be different, too, though they probably overlap. So no two innate responses will be exactly the same. Different individuals’ genetic makeup will also play a role. Now, we know that the link between the innate and the adaptive (antibodies, T cells) immune responses are the dendritic cells. They ingest fragments of the invaders and, influenced to mature and differentiate by the local chemokine and cytokine soup, leave the inflammatory site and travel to the lymph nodes, where they show their burden of antigen to the adaptive immune system’s T cells for evaluation and response. What I want to suggest is that no two arriving dendritic cells will be exactly alike, as they matured in different microenvironments. Thus they may stimulate the T cells which contact them differently, and this could result eventually in very different kinds of immune responses. For example, in one case the response may be mostly antibody, and in another, mostly T cell-mediated, as in Poison Ivy. Is it possible some pathogens have learned how to manipulate the immune system so that the response against them is ineffective? I’m thinking about HIV: everybody who is infected makes antibody to the virus, but it isn’t protective. T cell responses would be protective, the way they are to other viruses, but against HIV they are very weak.