Sera of patients with systemic lupus erythematosus cross‐neutralizes dengue viruses

Abstract

Dengue is the most prevalent mosquito‐borne disease in Southeast Asia, where the incidence of systemic lupus erythematosus (SLE) is approximately 30 to 53 per 100,000. Severe dengue, however, is rarely reported among individuals with SLE. Here, whether sera of patients with SLE cross‐neutralize dengue virus (DENV) was investigated. Serum samples were obtained from individuals with SLE who were dengue IgG and IgM serology negative. Neutralization assays were performed against the three major DENV serotypes. Of the dengue serology negative sera of individuals with SLE, 60%, 61% and 52% of the sera at 1/320 dilution showed more than 50% inhibition against dengue type‐1 virus (DENV‐1), DENV‐2 and DENV‐3, respectively. The neutralizing capacity of the sera was significantly greater against DENV‐1 (P < 0.001) and DENV‐3 (P < 0.01) than against DENV‐2 (P < 0.05). Neutralization against the DENV correlated with dengue‐specific IgG serum titers below the cut‐off point for dengue positivity. Depletion of total IgG from the sera of patients with SLE resulted in significant decreases of up to 80% in DENV inhibition, suggesting that IgG plays an important role. However, some of the SLE sera was still able to neutralize DENV, even with IgG titers <0.1 OD absorbance. Our findings suggest that sera of patients with SLE contain IgG, and possibly other type of antibodies, that can cross‐neutralize DENV, which may explain the rarity of severe dengue in individuals with SLE. Further studies, are needed to further substantiate this finding and to elucidate the specific neutralizing epitopes recognized by the sera of individuals with SLE.

Viral Infections and Systemic Lupus Erythematosus: New Players in an Old Story

“…The relationship between Dengue virus (DENV) and SLE is complex and still remains to be elucidated. On the one hand, DENV has been anecdotally reported to trigger SLE and LN [46]; on the other hand, IgG that can cross-neutralize DENV are often found in SLE sera, probably explaining rarity of severe forms in SLE patients [195].…”

Dengue hemorrhagic fever with bleeding and fluid overload in a patient with active lupus nephritis: a case report of diagnostic and therapeutic challenges

“…The authors suggest that a different approach without restriction may need to be considered for more severe leakers. However, it is interesting to note that patients with SLE have been hypothesized to have only mild dengue infection due to neutralization of the dengue virus with various types of antibodies found in SLE patients [ 6 ]. If this is in fact the case, perhaps a restrictive fluid approach could be tried on all dengue patients with lupus nephritis, but it is difficult to give general instructions without detailed studies in this regard.…”

Immunoglobulin M seroneutralization for improved confirmation of Japanese encephalitis virus infection in a flavivirus-endemic area

“…This has also been demonstrated for DENV infections. 42 , 43 It is notable that as JE is predominantly a neurological infection, and the natural history of the immunological response is different to flavivirus infections presenting as acute febrile syndromes, by the time of clinical presentation, anti-JEV IgM and IgG is detectable in a larger proportion of patients. Therefore use of the IgM-VNT method for JE confirmation is a logical approach.…”

“… 37–41 A modification of VNT, involving prior depletion of IgG, has been successfully performed for ZIKV 19 and DENV infections. 42 , 43 The underlying principle is that long-lasting IgG responses from vaccination and previous infection are major contributors to non-specific VNT results. IgG removal results in detection of specific neutralizing IgM antibodies, which are markers of acute infection.…”