Friday, May 06, 2011

Immunodeficiency of CLL explained

It may help to explain my post from yesterday if I put more in lay language. There seem to be two processes going on to account for the immunodeficiency that we see in indolent lymphomas. For all lymphomas, whether node based or not, there seems to be an underlying inflammatory phase (a good example would be the H.pylori infection behind gastric lymphoma). Helper T cells get attracted to the inflammatory reaction and activated to help in antibody production (Th2 cells). As a result there is a shortage of naive T helper cells to be directed to other tasks like responding to Hepatitis B vaccine. The second type of immunosuppression occurs where there are circulating tumor cells as in CLL. Here, cell to cell contact between CLL cells and T helper cells affects the T helper cell finction so that they are unable to make the normal T helper cytokines and start to die, so there is an absolute deficiency of T helper cells and therefore an inability to respond to vaccines.

People should now come up with ideas to remedy this.


Anonymous said...

For the first case, would a high sensitivity CRP test be useful in detecting the inflamation?

Terry Hamblin said...

I doubt it. CRP just means activated IL-6 and the degree of activation would be too small.

Abe said...

Hello Terry
Thank you for all the CLL information. I have smoldering CLL but am remarkably stable and healthy after 11 years. My hematologist seemed a bit put off last time when I told him I do not bother with influenza immunization. Has it been established if immunization could actually be harmful to us? You(they)stated "This pattern may be seen in late CLL but not in early CLL" Are you saying that in some cases immunization may still be beneficial? (yes, I do have a lot of trouble with inflammations). Thank you, Abe

Terry Hamblin said...

Influenza vaccination is quite harmless. Some people may respond.

Nick said...

Thank you for the articles

Understanding that there are two patterns to immunodeficiency in CLL has been revealing. It is good to read about an area of CLL consequence that is relevant to all of us when living with CLL. Can both patterns occur together; for example in early stage CLL accompanied by an inflammatory condition such as SLE or RA or in more advanced CLL alone?

On a slightly different topic; The fatigue/feeling unwell often experienced with early CLL has also been explained by T cell contact with leukaemic B cells, but this is removed as the CLL develops immunodeficiency is this Pattern 1 immunodeficiency? Is the second pattern: down regulation of TCR signalling and cytokine secretion part of the same mechanism in early CLL fatigue?

I am understanding that both patterns effect vaccination efficacy. I was told by the clinician administering my vaccinations last winter that I would remain vulnerable for five days or so before the vaccination was effective. But came down with the worst flu and chest infection I had ever experienced three days after vaccination. I had surmised that I contracted the virus from the germ soup of the waiting area, can vaccination itself create a reaction? Or do you think I was just unlucky.

Nick said...

Dear Professor Hamblin.

Reading your two recent CLL immunodeficiency bloggs , raised some questions in my basic understanding. I posted a reply but reading back my message it may appear a bit garbled, I think what I was asking was can both patterns occur together in early CLL when CLL is accompanied by another inflammatory condition?

Terry Hamblin said...

I guess both patterns could occur together if the conditions were right.

I don't think that the precise mechanism for CLL fatigue is well understood.

I think you were just unlucky with your infection. I would not have expected it to be a consequence of teh vaccination.

Nick said...

Hello Dr Hamblin,
Thank you for your answers.I was drawn back to vaccination efficacy, having learned that use of Ranitidine (Zantac), is apparently a CLL’ers trick to improve vaccination efficacy? I was told that this never became mainstream, but you were very interested in this. Can you explain what current thinking is?



Terry Hamblin said...

This comes from a Danish paper some years ago. Dr Jurlander did some experimants with Haemophilus influenzae vaccination. (note not the influenza virus) He gave a big dose of Zantac (300mg twice daily) for 90 days with vaccination on days 1 and repeated on day 45. This markedly improved the response. The study has not been repeated but some CLL people have tried it.