• Autoimmune Diseases
• Sjøgren's Syndrome
• Systemic Lupus Erythematosus
• B cells

Stone and his coworkers present two elegant papers on IgG4-related disease (IgG4-RD).1

In ‘The Diagnostic Utility of Serum IgG4 Concentrations in IgG4-Related Disease’, Carruthers et al2 retrospectively analysed charts of 190 patients with elevation of IgG4. They also randomly selected 3360 charts with normal IgG4 levels and reviewed 190 cases for characteristics of IgG4-RD. They found:

• The specificity and positive predictive value of elevated serum IgG4 concentrations were only 60% (183/309) and 34% (65/190), respectively.

• When the IgG4 value ‘cut-off’ values were doubled1 so as to improve specificity, the sensitivity of IgG4 levels fell to an unacceptably low 35%.

In a closely related study by the same group, Wallace et al describe the ‘Diagnostic Utility of Plasmablasts as a Biomarker for IgG4 Related Disease (IgG4 RD) Independent of Serum IgG4 Levels’.

• They reported 37 patients with biopsy-proven IgG4-RD.

• Thirteen of these patients had normal IgG4 levels.

• But all 37 patients had elevated levels of plasmablasts (CD19 low, CD20 neg, CD38+ and CD27+).

• They also demonstrated that rituximab (anti-CD20 antibody) was beneficial, even though the plasmablasts were CD20 negative, indicating removal of plasmablast precursors.

Since we see patients with possible IgG4-RD in a variety of organs (table 1) that are often not easy to biopsy, serum IgG4 levels have incorrectly become a ‘surrogate’ marker for IgG4-RD in clinical practice.3 ,4 These articles will make us take a hard look at our current diagnostic approach to IgG4-RD.

The spectrum of IgG4-RD is remarkably complex (table 1) and it would be nice to simply think of this complex multisystem pathology as a single pathogenetic disorder occurring in a variety of target organs.

Unfortunately, it may not be that simple.

In a critical evaluation of the evolving …