Seronegativity for Dummies: A Lesson in Seronegative Blood Results

How many times have you heard of doctors relying solely on blood results and not enough on the physical symptoms? How many times has your family ignored your doctor(s) claims of illness despite blood markers because it’s “unheard of?” How many of you were confused when your doctor told you there was nothing wrong because you showed no Rheumatoid Factor or Positive ANA, but you felt horrible? How many of you never actually understood the science and reason behind seronegativity? How many of you don’t even know what Seronegative means?

A Lesson in Seronegativity: ANA, Rheumatoid Factor, CRP and ESR.

When I was first diagnosed, I was told I had Seronegative Autoimmune Disease, most likely Rheumatoid Arthritis (though others still remain in the mix). I was told that 70 years ago this disease was a life sentence and crippled and killed its victims, but now there were treatments and remission. I thought within a few month’s time and with some pills, I’d be better. I took it head on. My family didn’t take it at all. The lack of a Rheumatoid Factor meant I couldn’t possibly be sick. It left a doubt: is this really the diagnosis? Will it change in a year’s time? What if they’re wrong? It took opinions from three different doctors and excessive suffering before my family accepted the illness for what it was. I remember the first call I got being told my SED rate and CRP were elevated above normal levels. My response to the nurse on the phone “So I’m NOT crazy!” I was elated. But for some, seronegativity creates doubt and confusion, perhaps denial.

What does Seronegative mean?

• Seronegative means that your blood does not produce the antibodies that show up when tested for various autoimmune diseases, such as Lupus or Rheumatoid Arthritis. The most common antibodies to show up are called Anti-Nuclear Antibodies and the Rheumatoid Factor. Both are indicators of autoimmune disease, but as well all know autoimmune diseases are rarely by the book. It is possible to have these diseases without showing positive blood work. That is when your symptoms and inflammation rates (SED rates and C-reactive protein) come into play.

• If you know in your heart that something is wrong, do not stop searching for answers. It’s unfortunate, but not uncommon for physicians to make decisions and diagnoses based strictly on blood tests. While there is nothing wrong with having faith in medical testing, there are exceptions. They are not all that rare, either.

How common is Seronegativity?

• Not uncommon at all, though it is often misunderstood or not recognized (and this usually results in a misdiagnosis or no diagnosis at all). About 30% of Rheumatoid Arthritis patients are seronegative, which is not too small a percentage when you consider the amount of people affected by RA. Seronegative Lupus is not nearly as common as S-RA, but it is possible and does happen. This seronegativity can occur in hoards of different diseases, from Rheumatoid Arthritis to HIV to Lyme Disease. Still’s Disease, RA’s very complicated/rare sister-disease, is distinctly marked by seronegative findings, which make diagnosis even harder.
  

What does seronegativity mean for your disease course? Is there a difference between seronegative and seropositive patients?

• Generally seronegative patients do not develop Rheumatoid Nodules, but there are always exceptions to this finding. There is also speculation that seronegativity is an indicator of less severe disease and slower progression, but again, there are exceptions. I am one of them. It is so so important to remember that whenever you read any online health article that you keep in mind no patient is the same. I have a fast progressing severe case of Rheumatoid Arthritis, yet I am seronegative. Someone else might have joint pain here and there, no other symptoms, and be seropositive. Never compare yourself to others or studies, because those studies did not study you. Be educated and knowledgeable, but do not put yourself into those articles. This one included.

Once seronegative, always seronegative?

• No. Seronegativity can changes and often does. I am tested regularly for RF and a positive ANA (among other antibodies) because with disease progression and immunological changes, your blood results may change. You can also be seronegative for one disease and seropositive for another.

What is SED rate and C-Reactive Protein?

• SED rate (aka ESR), or your erythrocyte sedimentation rate, is an indicator of how high (or low) the inflammation is in your body.It is nonspecific, meaning it does not indicate where the inflammation is in one’s body.
  
  
• C-Reative Protein (CRP)— another indicator of acute inflammation in the body. It is also used as a measure for heart disease risk. Those with high CRP rates are at an increased risk of having a stroke, heart attack, or developing vascular diseases.

What is Rheumatoid Factor?

• Rheumatoid Factor— Your Rheumatoid Factor (RF) is an autoantibody, simply put: a protein that is produced by the immune system. Autoantibodies are what attack your own tissues by mistake. Presence of RF indicates autoimmune disease, such as Rheumatoid Arthritis, however an absence of RF does not mean one is disease-free.

What is ANA?

• ANA or Anti-Nuclear Antibodies  are autoantibodies “directed against […] the cell’s nucleus.” Like RF, they are markers of inflammation and autoimmune disease. An ANA test is performed using an immunoflorescent technique— light microscopy using florescent dyes to examine different cell substances— and results are measured in titers (measure of concentration).
  
  
  
• A normal titer is about 1:40 or lower. Higher titers are indicative of an abundance of these autoantibodies and thus, autoimmune diseases, most commonly Lupus, but also in Rheumatoid Arthritis, Sjogren’s Syndrome, and multiple other conditions
  
  
• You can have a positive ANA and be completely healthy or you can have a negative ANA and be ill.

Can you have seronegative inflammation markers and still have an inflammatory disease?

• Yes. Whether you have RA or Lupus, you can have negative SED rates or C-Reactive protein rates. 
• In Lupus patients, tests for CRP may be completely normal unless synovitis (inflammation of the synovium, the lining of the joints) is present.
• Meaning that one can have serious inflammation, be in excruciating pain, and still seem completely normal. This finding is often overlooked, not understood, and puts patients in the dark thinking they are crazy.
• So if this is the case, it’s important for patients and doctors alike to realize that having seemingly normal lab results does not mean a patient is in remission.

Further Reading:

• Antinuclear antibody-negative lupus…does it no longer exist?
• Seronegative Systemic Lupus Erythematosus (abstract)
• The Many Myths of Erythrocyte Sedimentation Rate and C-Reactive Protein
• Erythrocyte Sedimentation Rate, C-Reactive Protein, or Rheumatoid Factor Are Normal at Presentation in 35%–45%…