Table 2.
Patients’ characteristics and additional value of testing RF isotypes
| Study | Nephelometry/latex test | IgM | IgA | IgG | Median age of patients (range or SD) | Time from diagnosis | Median age of controls (range or SD) | Notes |
| Visser 199617 | Yes | No | No | No | 60 (16–89) | 6 months (median) | 47 (12–92) | |
| Saraux 200219 | Yes | Yes | No | No | 49 (33–65) | n.a. | n.a | Combination more predictive of RA: nephelometry+IgM RF (sensitivity+15%, specificity −7%). |
| Bas 200218 | Yes | Yes | Yes | – | 64 (22–87) | n.a. | 58 (4–191) | IgM-RF+IgA-RF: increased LR for RA. |
| Bas 200330 | – | No | Yes | – | 54 (22–77) | n.a | 42 (4–101) DC 60 (50–75) HC |
CCP+IgA-RF: increased specificity for RA diagnosis (CCP specificity 90%, IgA-RF 90%, IgM-RF 82%; CCP+IgA RF 98%; CCP+IgA-RF+IgM RF 98%). |
| Rantapää-Dahlqvist 200320 | – | No | Yes | No | 54 (31–77) | 3 years (median) | 55 (30–69) | IgA-RF predicts RA diagnosis. |
| Vallbracht 200447 | – | No | No | No | 62 (±15) | n.a | 56 (±18) 52 (±19) 50 (±20) |
|
| Greiner 200526 | Yes | – | n.a. | – | 58.6 (19–84) | n.a. | n.a | |
| Mikuls 200627 | – | Yes | Yes | No | 51 (±13) | <2 years | 45 (±14) HC 39 (±12) SLE |
CCP sensitivity 62%, specificity 94%. IgM-RF sensitivity 70%, specificity 80%. IgA-RF sensitivity 65%, specificity 87%. IgG-RF sensitivity 38%, specificity 85%. CCP+IgM RF sensitivity 55%, specificity 98%. CCP+IgA RF sensitivity 59%, specificity 98%. |
| Bobbio Pallavicini 200716 | Yes | n.a. | n.a. | n.a. | 57 (±12) | 8.3 (±6.9) | n.a. | |
| Jaskowski 201022 | Yes | Yes | No | No | n.a. | 8.6 years (mean) | 33 (16–70) | In 48 CCP-negative subjects, 57% were FR positive (IgM-RF+IgA RF or triple positive). |
| Nell-Duxneuner 201014 | Yes | – | No | No | 50 (18–83) | < 3 months | 43 (18–87) | |
| Brink 201621 | – | Yes | No | No | 50.3 (IQR 20.1) |
6.2 years (median) | 51.1 (IQR 20) |
In pre-symptomatic individuals, OR IgM-RF 11.1, IgM-RF+IgA RF 21.9, IgM-RF+IgA-RF+IgG RF 34.5. OR CCP 20.2. OR CCP+IgA RF 50.7, CCP+IgG RF 30.2, CCP+IgM RF 67.6. |
| Sieghart 201823 | Yes | Yes | Yes | No | 57 (47–66) EA 53 (44–63) RA |
<3 months >2 years |
55 (43–64) DC 50 (42.55) HC |
14/290 (4.8%) patients negative at nephelometry resulted positive for IgM-RF. 14/109 (12.8%) ACPA-IgM-RF negative were IgA-RF+. |
| Elshafie 201915 | – | Yes | Yes | Yes | 49 (18–80) | 3 years (1–420 months) |
35 (n.a.) | CCP sensitivity 70.7%. CCP+IgM RF sensitivity 80.1%. CCP+IgM-RF+IgA RF sensitivity 89.5%. CCP+IgM-RF+IgA-RF+IgG RF sensitivity 100%. |
| Kelmenson 202024 | – | n.a. | n.a. | n.a. | 37 (±8) | 5.1 years | 37 (±8) | |
| Janssen 202028 | – | n.a. | n.a. | – | 55 (±11) | 5.5 years (3–10) | 42 (±15) DC 34 (±15) HC |
|
| Hermosillo-Villafranca 202125 | – | No | No | No | n.a. | n.a | n.a. | |
| Pertsinidou 202129 | – | n.a. | n.a. | n.a. | 57 M/54 F (18–70) | <2 months | n.a. | |
| Van Hoovels 202231 | – | Yes | Yes | No | 57 (18–86) | 16.8%<6 weeks 83.2%≥6 weeks |
53 (11–92) | IgA RF picked up 0.5% or 2.3% (Thermo Fisher or Orgentec assay, respectively) RA patients that were ACPA and IgM RF negative. Single IgA RF positivity was found in 1.5% or 5.6% (Thermo Fisher or Orgentec assay, respectively) of controls. CCP+high titers RF (IgA or IgM) LR 62-infinity. |
CCP, cyclic citrullinated peptide antibodies; DC, disease controls; EA, early arthritis; HC, healthy controls; Ig, Immunoglobulin; LR, likelihood ratio; n.a., not applicable; RA, rheumatoid arthritis; RF, rheumatoid factor; SLE, systemic lupus erythematosus.