Complement Pathway May Play a Role in SLE-Associated Thrombotic Microangiopathy

The complement pathway plays a complex role in patients with systemic lupus erythematosus (SLE) and thrombotic microangiopathy, according to new data presented at the American Society of Nephrology’s Kidney Week.

To determine whether activation of the complement pathway contributes to thrombotic microangiopathy, a life-threatening complication of SLE, the researchers enrolled patients with thrombotic microangiopathy in a prospective study at Peking Union Medical College Hospital in China. In all, 40 participants with thrombotic microangiopathy had SLE, 14 had lupus nephritis, and 38 had other kinds of thrombotic microangiopathy.

In addition to using ELISA to measure peripheral blood concentrations of adhesion molecules (ICAM1 and VCAM1), complement factor H, E-selectin, terminal complement complex (soluble C5b-9), and the relative activity of the complement pathway, the researchers performed whole-exome sequencing to determine the patients’ genetic variants.

As a result, they found that patients with SLE and thrombotic microangiopathy can be categorized into 2 subgroups with differing levels of severity depending on the presence or absence of microangiopathic hemolytic anemia (MAHA). Moreover, the presence of complement factor and E-selectin may help distinguish the 2 subgroups.

More specifically, patients with SLE whose thrombotic microangiopathy was confined to the kidney had a higher concentration of complement factor H than patients with SLE and atypical hemolytic uremic syndrome and a lower level of E-selectin than patients with SLE and atypical hemolytic uremic syndrome and MAHA.

In addition, patients with SLE and atypical hemolytic uremic syndrome had more severe hematological signs and symptoms and higher creatine levels than patients with SLE whose thrombotic microangiopathy was confined to the kidney.

Regarding genetic variants, the researchers found that treatment response in those with variants was worse than in those without them. Moreover, thrombophilia variants had greater influence on the genetic susceptibility to thrombotic microangiopathy than complement variants did. In addition, the VCAM1 level in those with complement-related genetic variants was significantly higher than in those without such variants.

“The complement pathway is highly activated in patients with compound complement mutations, resulting in increased complement factors consumption,” the researchers concluded.

—Ellen Kurek

Reference:

Quexuan C. Characteristics and genetic defects of systemic lupus erythematosus-associated thrombotic microangiopathy. Paper presented at: ASN 2021 Kidney Week; November 4-7, 2021; Virtual. https://www.asn-online.org/education/kidneyweek/2021/program-abstract.aspx?controlId=3611572