Pankti Mehta Profile picture
Clinical fellow @UHN @UofT | Immunology & Rheumatology| DSMC member @rheumjnl @IJRheum @IndianRheum | Alumnus @SGPGI (rheum) @KEMhospital (MBBS, Int Med)

Apr 18, 2023, 15 tweets

Rheumatoid factor

One of the most used & abused tests in #rheumatology

Let's learn a bit about its origin & utility!

#MedEd #MedTwitter #RheumTwitter

(1/15)

1️⃣ what is RF actually?🤷‍♀️

They are antibodies directed against the Fc fragment of IgG antibody

(2/15)

2️⃣ How & when was it first discovered?📆

1st described by Waaler in 1940, a factor present in 🚶‍♂️serum (in patients with RA & other diseases) that agglutinates 🐑 RBCs when sensitised with sub agglutinating doses of anti-🐑-RBC 🐰 immunoglobulin
onlinelibrary.wiley.com/doi/10.1111/j.…

(3/15)

The most active sera were from patients with RA, however, only 50 of 77 RA patients had a positive RF!
Hence he concluded ⏬

(4/15)

🌹 Rose further described in 1948 that high titres were found in patients suffering from active RA compared to those with rheumatic fever & other arthritis

Since it was first discovered in patients with RA, it was named as 'Rheumatoid Factor'

pubmed.ncbi.nlm.nih.gov/18863659/
(5/15)

The rose waaler test is now obsolete as we obviously don't want to deal with 🐑 & 🐰 now!

3️⃣ So, what methods are used to detect RF now?
(6/15)

🔹Latex agglutination

Replace RBCs➡️ latex particles!

✅ Simple
✅ Inexpensive
✅ Semiquantitative
✅ Sensitive

❎ Low throughput
❎ Semiquantitative
❎ Isotyping can't be done

To note, exact titre estimation & isotyping are not of relevance in the clinic!
(7/15)

🔹ELISA
🔹Nephelometry
🔹Turbidiometry

✅ Sensitive
✅ High throughput
✅Automated
✅ Quantitative
✅ Isotyping (ELISA)

❎ Expensive

(8/15)

4️⃣ does a positive RF= RA?

❗NO❗

RF is non specific & can be present in numerous other diseases.

Top off the list being

🔹Infections
🔹Other autoimmune diseases
🔹Chronic diseases
🔹Malignancies
🔹Even healthy individuals!

hindawi.com/journals/dm/20…
(9/15)

To note, a very high prevalence of RF is observed in

🔹Sjogren
🔹Hepatitis C
🔹PBC
🔹Type II cryoglobulinemia

(10/15)

5️⃣ what about the converse? Does a negative RF rule out RA?

Again, ❗NO❗

The sensitivity of RF for RA is 60-90%, so patients with RA can be negative for RF

(11/15)

6️⃣ Does seropositive & seronegative RA differ?

Yes in some aspects.

RF positivity is associated with a severe erosive disease & extra articular manifestations
(12/15)

7️⃣ is there a role of repeat RF testing during treatment ?

Please, ❗NO❗

RF may decline or turn negative with the use of Rituximab or TNFis but this decline has no clinical utility
(13/15)

8️⃣ what about IgA and IgG RF?

The majority of seropositive patients have IgM RF (>90%) & hence most commonly detected
pubmed.ncbi.nlm.nih.gov/3813676/

IgA>IgG RF are associated with

🔹Greater specificity for future development of RA in preclinical cases

🔹More severe disease
(14/15)

🔺BUT🔺

Isolated IgA/IgG RF positivity is highly uncommon.

Again, anti-CCP is an easily available specific assay for patients negative for IgM RF.

Hence the clinical utility of RF isotyping is minimal.

(15/15)

#MedTwitter

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