ANCA -- teaching the novice!

[KathyB]

Hi all,

I'm getting ready for another follow-up with my rheumy and infectious disease docs on Dec 7. Briefly, WG was diagnosed in late Aug and I have been through one 4-week Rtx regiment and looking ahead to another round late Feb. Prednisone is down to 20 mg/day and I'm still on meds recovering from nasty bout of fungal pneumonia. Also taking meds for high BP, but no WG maintenance drugs as yet. My kidneys are most impacted with limited respiratory involvement except for plugged/popping ears and runny nose with most activity. Fatigue still a huge factor with knee pain and lots of muscle weakness. I've started PT as well.

Okay -- so my doctors have talked about many levels & rates from bloodwork and urinalysis. Can anyone explain more about the ANCA tests? These seem to be important markers for indicating initial diagnosis and WG flaring, remission, etc. This area is foggy to me. Any help is appreciated!

KB

[Dirty Don]

From one novice to another, what I've learned both from docs and peeps on here, is that ANCA testing is not accurate, just an indicator. It can positive or negative and you still wouldn't really know if you had WG...it has to be in combo with other testing procedures. You really need the full blood tests, medical history, and symptom discussions with your docs.

Don

[pberggren1]

ANCA is always good to test but it is usually an unreliable marker for most people.

[Al]

Kathy, ANCA tests are accurate; it's the interpretation that is dicey. The test determines the titer of certain kinds of ANCA (most commonly anti-PR-3 for GPA, aka Wegener's, and anti-MPO for MPA) But ANCA are only "associated" with the disease, and need corroborating evidence--usually histological, which means that actual samples (like from a biopsy) have been looked at under a microscope. Here, ANCA show as C-ANCA (associated with PR-3) and P-ANCA (associted with MPO). Now, ANCA are Immunoglobulin G (IgG) antibodies, produced by B cells. There are four subclasses of IgG antibodies, and ANCA can fall into all four categories. But the ANCA test does not distinguish among the four kinds. If it did, the test might be a better indicator of disease activity. Current thinking is that ANCA are, in fact, directly involved in the disease process--but not, perhaps, all ANCA. For kidney involvement, IgG subtype 3 seems to be the nastiest, in that patients may be in remission with a relatively high ANCA titer, but not when there is a substantial population of subtype 3 ANCA. The other evidence is physiological: granulomas and such seen in important tissue samples. For GPA sufferers, those of the upper airway and ears (and often other parts) are legendary (and painfully obvious).

In my case, my ANCA are of the anti-MPO type (P-ANCA), and I have very little, if any, upper airway involvement. Heaviest hit are the kidneys, and, to a lesser amount, the lungs. Unlike many people on the forum, I don't have unbearable joint pain. Some, of course, but fortunately, I can deal with it without drugs--which is good, because I am disallowed NSAIDS (aspirin and such), and I don't really trust Tylenol. Heavy kidney involvement, by the way, requires a different maintenance protocol than many here are on. MTX is not kidney friendly, so generally AZA (Imuran) and MMF (CellCept) are prescribed.

You didn't say what type or types of ANCA showed up on your blood work, or what the pathologist said about any biopsy you have had. These would be interesting, though. From a clinical point of view, the strategy is one of triage: first, whack down the inflammation ASAP. This is where the massive amounts of the steroids come into play. (In some cases, like mine, plasma exchange is then employed to sweep out existing antibodies.) Then, keep the immune system from producing new ANCA. This is what CTX and RTX do, though the RTX is specifically targeted at the B cells. CTX more globally bashes the immune system.

The relationship of infection, which, of course, is what the immune system is largely concerned with, and our disease is rather complicated. For purposes of determining likelihood of a relapse, you need both a lot of ANCA around, and a lot of cytokines, which are released in massive numbers during infections. Of course, one of the purposes of immunosupressive therapy is to tamp down cytokine production--but that leads to the higher rsik of infection. So it is a double-edged sword, perhaps the most vexing part of designing a maintenance strategy.

I hope this helps!

Al

[elephant]

Very informative Al. Bravo!

[Thakator]

Yes, Al, bravo indeed. Thanks for taking the time to compile and to share this info.; I'm sure it will prove to be of great assistance to many. Kudos, Ron

[Dryhill]

Wow Al, and I thought I understood this wonderful illness of ours. You put me to shame.

Jim

[Al]

Wow Al, and I thought I understood this wonderful illness of ours. You put me to shame.

No shame in this world, Jim. Pain, yes, but no shame.

That is only the start of this ANCA business, of course. I left out a lot, but maybe this is enough to get the ball rolling.

Al

[KathyB]

Thanks, Al! Lots of info that will require more thought and explanation! I have heavy kidney involvement and was diagnosed from a kidney biopsy. They chose not to do the lung biopsy because they had what was needed from the kidneys. I already have polycystic kidney disease in left kidney which has left it functioning at minmal levels with the right kidney damaged/ruined 50% from WG. I remember the docs combining all the test results in making decisions. My creatinine had gone from 4.76 at its worst to now around 1.8 (waiting on most recent results, though). Of course, there are many other markers from blood work and urinalysis. I just hadn't really grasped the ANCA numbers. What tests does that include? I don't see anything on my printouts that say ANCA per se. I'm going to review all my other notes, too.

[KathyB]

I reviewed my discharge notes from September. Hemoptysis, Hematuria, and AKI: ANCA associated vasculitis (WG and Microscopic polyangitis). Renal biopsy report showed " pauci-immune GN."